Drug Accountability
(08/03/2007)

Question 1:

I have a question Pharmaceutical industry-sponsored clinical trials done under a hospital central IRB, with the study medication kept in an offsite location outside of the Hospital Pharmacy, mainly at the PI's private office. is there any regulations or guidances covering this issue, especially that the pharmacy will not be able to dispense or account for the study drug? and is the Investigational pharmacy responsible for the study drug?

I appreciate your prompt response, since I have to make a decision regarding this urgent issue.

Answer 1:

FDA's regulations place responsibility for control and accountability of supplies of the investigational drug on the sponsor (see 21 CFR 312.57(a), 312.58(b), and 312.59) and the clinical investigator (see 312.61, 312.62, and 312.69):

Sec. 312.57 Recordkeeping and record retention. (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.

Sec. 312.58(b) Controlled substances. If an investigational new drug is a substance listed in any schedule of the Controlled Substances Act (21 U.S.C. 801; 21 CFR part 1308), records concerning shipment, delivery, receipt, and disposition of the drug, which are required to be kept under this part or other applicable parts of this chapter shall, upon the request of a properly authorized employee of the Drug Enforcement Administration of the U.S. Department of Justice, be made available by the investigator or sponsor to whom the request is made, for inspection and copying. In addition, the sponsor shall assure that adequate precautions are taken, including storage of the investigational drug in a securely locked, substantially constructed cabinet, or other securely locked, substantially constructed enclosure, access to which is limited, to prevent theft or diversion of the substance into illegal channels of distribution.

Sec. 312.59 Disposition of unused supply of investigational drug. The sponsor shall assure the return of all unused supplies of the investigational drug from each individual investigator whose participation in the investigation is discontinued or terminated. The sponsor may authorize alternative disposition of unused supplies of the investigational drug provided this alternative disposition does not expose humans to risks from the drug. The sponsor shall maintain written records of any disposition of the drug in accordance with 312.57.

Sec. 312.61 Control of the investigational drug. An investigator shall administer the drug only to subjects under the investigator's personal supervision or under the supervision of a subinvestigator responsible to the investigator. The investigator shall not supply the investigational drug to any person not authorized under this part to receive it.

Sec. 312.62 Investigator recordkeeping and record retention. (a) Disposition of drug. 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.

Sec. 312.69 Handling of controlled substances. If the investigational drug is subject to the Controlled Substances Act, the investigator shall take adequate precautions, including storage of the investigational drug in a securely locked, substantially constructed cabinet, or other securely locked, substantially constructed enclosure, access to which is limited, to prevent theft or diversion of the substance into illegal channels of distribution.

Generally, the details of how the study drug is to be handled would be spelled out in the study protocol.

For institutions and IRBs, the pertinent regulations would be 21 CFR 56.109(a), which states that an IRB "shall review and have authority to approve, require modifications in (to secure approval) or disapprove all research activities covered by these regulations..." and 21 CFR 56.109(f), which states an IRB "...shall have authority to observe or have a third party observe ... the research..."

If the institution or IRB that reviewed and approved the study is concerned about an investigator's ability to control access to the study drug, or his ability to account for supplies of the investigational drug, the institution and/or the IRB may impose additional requirements on the investigator. There are many ways this could be done--for example, the institution's/IRB's SOPs might require the investigator or a third party to provide periodic accounting of the supplies of the study drug, or the institution/IRB could arrange for audits of the investigator's records and drug storage facilities, or the institution/IRB could require the drug to be dispensed from the hospital pharmacy. I'm sure there are other ways as well. In any event, FDA's regulations are general and not detailed as to how supplies of the study drug should be accounted for, so sites, sponsors, IRBs and institutions have the flexibility to work out their own procedures to best accommodate the particular situation.

Question 2:

I would like to thank you for taking the time to respond to my question in such details. I appreciate the information that you have provided. As I had suspected the FDA provides for a general guidance regarding the conduct of clinical studies without delving in the legalities governing the different departments.

Thank you so much for assistance in clarifying this issue.

Answer 2:

You didn't say exactly why you were asking the question, but you might also want to consult with the institution's legal staff to look into the liability question.


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