Research with Drugs/Biologics

An IND (Investigational New Drug) application to the FDA is required when a drug or biologic is not approved for marketing in the US and is intended to be used in a clinical investigation. An IND may also be required for a clinical investigation of marketed (commercial) drugs or biologics unless the drug or biologic qualifies for IND Exemption.

FDA regulations allow clinical investigations on drugs to proceed without submitting a formal IND application if all of the following IND Exemption criteria are met:

• The drug used in the investigations is lawfully marketed in the United States;
• The investigation is not intended to be reported to FDA as a well-controlled study in support of new indication for use nor intended to support any other significant change in the labeling for the drug;
• The investigation is not intended to support a significant change in the advertising of the product;
• The investigation does not involve a route of administration or dosage level, use in a participant population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product;
• The investigation is conducted in compliance with the requirements for IRB review and informed consent [21 CFR parts 56 and 50]; and
• The investigation is conducted in compliance with the requirements concerning the promotion and sale of drugs [21 CFR part 312.7], e.g., the drug may not be represented as safe or effective for the purposes for which it is under investigation, nor may it be commercially distributed or sold.

See also the FDA Guidance on Determining Whether an IND is Required.

When the dietary supplement is being used in a study to diagnose, cure, mitigate, treat, or prevent a condition or disease, the supplement would be considered a drug and requires an IND from the FDA. For example, a clinical investigation designed to evaluate a dietary supplement's ability to prevent osteoporosis or to treat chronic diarrhea or constipation would need to be conducted under an IND.

If the study is limited to evaluating the dietary supplement's effect on the structure or function of the body but NOT diagnose, cure, mitigate, treat or prevent a disease, the dietary supplement is not a drug. For example, a clinical investigation designed to study the relationship between a dietary supplement's effect on normal structure or function in humans (e.g., guarana and maximal oxygen uptake) or to characterize the mechanism by which a dietary supplement acts to maintain such structure or function (e.g., fiber and bowel regularity) would not need to be conducted under an IND.

Participants who may receive drugs with significant potential for addiction (e.g., opiates, cocaine, alcohol, etc.) in a study must be informed that the drug they may or will receive are known to have a significant potential for addiction in some individuals. If the magnitude of the risk of addiction in relevant populations is known, it should be specified. The following risk mitigation measures should also be implemented:

• With some exceptions, potential participants who have a known history of addiction should be excluded from studies of drugs with a significant potential for addiction.
• Potential participants who have direct physical access to and routine handling of addicting drugs in the regular course of their work duties should be excluded from studies of drugs with a significant potential for addiction and to which the participant has access.
• The informed consent should indicate that potential participants should not participate in the study if they have any history of addiction to a drug or to alcohol.
• Participants should be asked to check off a box on the consent form to indicate that they do not have such a history.
• Investigators should consider whether to perform urine drug screening of participants.
• Investigators should consider incorporating a confidential pre-screening questionnaire about prior drug use history in such studies.
• If pre-screening questionnaires or urine testing is utilized, participants should be informed as to how the confidentiality of these data will be maintained, and to whom they may be released.

The exceptions to this exclusion policy are those protocols which require the participation of addicted persons to answer a scientific question (e.g., the effect of moderate doses of alcohol on a biologic variable which might predict subsequent relapse or give insight into the etiology of the disorder.) The justification for experimental ingestion or intoxication must be included in the protocol application.

It is known clinically that addiction to certain types of medications is an occupational hazard of certain groups of health care workers. Although the prevalence within each group is not well-established, it is a well-described hazard for personnel who meet the following functional definition: personnel with direct physical access to and routine handling of addicting drugs in the regular course of their work duties. In particular, there is a risk for addiction to opiates, sedative-hypnotics, and cocaine. The health care workers in this group generally include those with regular access such as: anesthesiologists; emergency room physicians; ward, operating room, post-anesthesia care unit, emergency room, and intensive care unit nurses; pharmacists.

Health care workers who would be excluded under this policy make up a small component of the available participant pool for the testing of new therapeutic drugs. Thus, their participation is not required to ensure proper testing and validation of the safety of new or existing addicting drugs. Therefore, any risk of addiction in this group, no matter how small, cannot ordinarily be justified by the scientific benefit to be gained by their participation in studies of addicting drugs. If an investigator believes that inclusion of such personnel is necessary for the scientific goal of the study, a special application that justifies inclusion of these personnel must be made in the submission to the IRB.

Any study to be conducted in California involving a Schedule I or Schedule II controlled substance must be submitted to the Research Advisory Panel of California for review and approval. RAP-C approval is required before any research study can be started, and before any research subjects can be screened or enrolled.

Research involving an investigational drug or biologic that will not be stored and dispensed by a licensed pharmacy or hospital department will need an approved SCAP. The SCAP should be approved before the project is submitted to the IRB, and documentation of the approved SCAP should be provided with your protocol submission in eProtocol. To initiate the process, complete the Security and Controlled Access Plan (SCAP) Intake Form.

The Orphan Drug Designation Program provides orphan status to products intended to treat diseases or conditions that affect small (rare) populations. The use of an orphan drug is regulated by the FDA under 21 CFR 316.

IRB approval is needed prior to using an orphan drug. A protocol application is required, a consent form must be reviewed, and available supporting documents must be provided, such as the Investigator’s Brochure and the Sponsor Protocol. In addition, the investigator must provide certification that the drug is considered an orphan drug by the FDA.

• Protect the rights, safety, and welfare of participants under the PD's care;
• Personally conduct or supervise the studies;
• Ensure the studies are conducted in accordance with the relevant, current protocol(s) and only make changes in a protocol after notifying the sponsor, except when necessary to protect the safety, the rights, or welfare of participants;
• Inform participants that the drugs are being used for investigational purposes and ensure that the requirements relating to obtaining informed consent and IRB review and approval are met;
• Report to the sponsor adverse experiences that occur in the course of the investigation(s) in accordance with §312.64;
• Ensure that all staff assisting in the conduct of the studies are informed about their obligations in meeting the above commitments; and
• Ensure that an investigation is conducted according to the signed statement, the investigational plan, and applicable regulations.

• Understand the information in the investigator's brochure, including the potential risks and side effects of the drug;
• Maintain control of drugs under investigation;
• Administer the drug only to participants under the PD's personal supervision or under the supervision of a sub-investigator responsible to the PD;
• Do not supply the investigational drug to any person not authorized to receive it;
• Maintain adequate records of the disposition of the drug, including dates, quantity, and use by participants; and
• If the investigation is terminated, suspended, discontinued, or completed, return the unused supplies of the drug to the sponsor, or otherwise provide for disposition of the unused supplies of the drug under 21 CFR §312.59.

• Prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation;
• Ensure case histories for each individual document that informed consent was obtained prior to participation in the study; and
• Retain records for a period of 2 years following the date a marketing application is approved for the drug for the indication for which it is being investigated; or, if no application is to be filed or if the application is not approved for such indication, until 2 years after the investigation is discontinued and FDA is notified.