Investigational Drugs and Drug Accountability
1. The IND Process
2. Code of Federal Regulations regarding investigational drugs
3. ICH (International Conference on Harmonisation) Guidelines for drug accountability of
investigational products
4. Investigational Drug Services at MUSC
5. Tips for adequately maintaining drug accountability records
The Investigational New Drug (IND) Process (from 21 CFR 312)
Before a drug can be marketed and sold in the United States, the sponsor of that product must
submit an IND application to the Food and Drug Administration. The FDA then assigns the drug
product a number, which is used to track the status of the drug.
An IND is NOT needed in the following situations:
1. The investigation is not intended to be reported to the FDA as a well-controlled study in
support of a new application nor intended to be used to support any other significant
change in the labeling of this drug.
2. If the drug is lawfully marketed as a prescription drug product, the investigation is not being
used to support a significant change in advertising for the product.
3. The investigation does not involve a route of administration or dosing level or use in a
patient population or other factor that significantly increases the risks associated with the
use of the drug product.
4. The investigation is conducted in compliance with the federal and institutional requirements
(e.g. IRB review, informed consent)
For investigator-initiated studies, an individual investigator may be asked (either by the sponsor or the
IRB) to apply for an IND if a study calls for the use of the drug outside of its usual labeling where there
may be potential for increased risk (e.g. using a higher dosage, different patient population, different
indication)
An IND application requires the following:
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Cover Letter
1571 and 1572
Copies of CVs of investigators
Copy of the protocol
Copy of the Investigator’s Brochure
The FDA has 30 days to respond to your request for an IND. If the FDA thinks an IND is required, they
will provide the investigator with an IND number. If the FDA does not think an IND is required, they do
not accept the application.
Investigational Drugs (21 CFR 312)
Labeling: The immediate package of an investigational product intended for human use must bear a
label with the statement: “Caution: New Drug—Limited by Federal (or United States) law to
Investigational use.”
Marketing: A sponsor or its representative (e.g. Drug Rep) is not allowed to represent in a promotional
context that the investigational product is safe or effective for the purposes for which it is under
investigation.
Charging: Charging for an investigational drug in a clinical trial under an IND is not permitted without
the prior written approval of FDA.
Investigator Responsibilities: The 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,
the investigator shall return the unused samples or otherwise dispose of them under the direction of the
sponsor.
ICH Guidelines for Accountability of Investigational Products (ICH 4.6)
1. Responsibility for investigational product(s) accountability at the trial site rests with the
investigator/institution.
2. Where allowed/required, the investigator/institution may/should assign some or all of the
investigator’s/institution’s duties for investigational product(s) accountability at the trial site
to an appropriate pharmacist or another appropriate individual who is under the supervision
of the investigator/institution.
3. The individual designated by the investigator/institution should maintain records of the
product’s delivery to the trial site, the inventory at the site, the use by each subject, and the
return to the sponsor or alternative disposition of unused product(s). These records should
include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the
unique code numbers assigned to the investigational product(s) and trial subjects.
Investigators should maintain records that document adequately that the subjects were
provided the doses specified by the protocol and reconcile all investigational product(s)
received from the sponsor. KEEP YOUR SHIPPING RECORDS!!!
4. The investigational product(s) should be stored as specified by the sponsor and in
accordance with applicable regulatory requirements.
5. The investigator should ensure that the investigational product(s) are used only in
accordance with the approved protocol.
6. The investigator, or a person designated by the investigator/institution, should explain the
correct use of the investigational product(s) to each subject and should check, at intervals
appropriate for the trial, that each subject is following the instructions properly.
Investigational Drug Services (IDS) at MUSC:
Contact Information: 792-9643; MUSC Pager: 11269
1. All inpatient medication trials MUST go through Investigational Drug Services (IDS).
2. For outpatient studies, it is up to the investigator whether the investigator wants to use IDS
3. If IDS is used, the investigator (or designee) should meet with IDS staff to go over the study
requirements—It is helpful to bring the following:
a. Copy of the protocol
b. Copy of the IRB approval and informed consent(s)
c. Drug accountability forms provided by the sponsor
d. List of contact information
4. Requests for study drugs must come in the form of prescriptions, with one person per
prescription—IDS can help develop these if required
5. Important to request medications as soon as you know they are needed—DON’T WAIT
UNITL THE LAST MINUTE!!
6. For monitor visits, important to let IDS know as soon as you do when the monitor is
coming—it is recommended to have the monitor schedule an appointment with IDS staff to
review accountability records
7. Important to note that although IDS would be designated by the investigator to dispense
and maintain records of study medications, the investigator is ULTIMATELY responsible
8. Someone from IDS is on call 24/7 to handle issues that arise.
Drug Accountability/Dispensing Tips:
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Keep all packing slips!
Review accuracy of packing slips—let sponsor know if accurate
Review shipping for damaged drug/packaging
Periodically review inventory—check for expiration dates, make sure you have enough drug
kits or dosage levels to complete the trial for the next several months
Count returned medications while the participant is still there so that you can question
participant about discrepant information
Store study medication in a secure location
Instruct participant to return all unused drug and packaging at each visit
Make sure study medication is labeled such that you know whose medication is whose
Make sure participant knows both brand and generic name of investigational drug (if
applicable)
Use a pill counting tray to count meds and try not to touch medication (if applicable)
11. Report lost or stolen medication to sponsor immediately—the sponsor may ask participant
to file a police report!
12. Document dispensing medication the day it is dispensed
13. Have a double check system where someone else has to check that you are giving the right
medication to the right person
14. Often easier to prepare medication before the participant arrives
15. Develop your own drug accountability forms if you don’t like the ones the sponsor uses
(although you may be required to fill out both!)
16. Controlled substances have different rules! Make sure you understand them! Internal audit
will review records of controlled substances semi-annually. Place where meds are kept
must be inspected by DHEC.