Drugs and Biologics Used in Clinical Research
Per FDA, Clinical investigation means any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or is not subject to requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be submitted later to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit.
FDA Requirements for New Drugs and Biologics
"Investigational new drug" (IND) means a new drug or biological drug that is used in a clinical investigation. The term also includes a biological product that is used in vitro for diagnostic purposes. The terms ''investigational drug'' and ''investigational new drug'' are deemed to be synonymous for purposes of determining whether a Notice of Claimed Investigational Exemption for a New Drug must be submitted to the US Food and Drug Administration (FDA).
- Before a new drug or biologic may be tested on humans, the sponsor (usually a pharmaceutical company, but sometimes an individual) must submit a Notice of Claimed Investigational Exemption for a New Drug to the FDA.
- FDA regulations [21 CFR 312.22 and 312.23] contain the general principles underlying the IND submission and the general requirements for an IND's content and format.
- After the sponsor submits an IND, there is a 30-day waiting period during which the FDA reviews the application to make certain subjects are not exposed to any unwarranted risks.
- Clinical studies can be initiated after the 30-day waiting period expires, unless a clinical hold is placed by the FDA. A clinical hold is an order issued by the FDA to the applicant to delay a proposed clinical investigation or to suspend an ongoing investigation.
- The FDA notifies the sponsor during the 30-day waiting period if a clinical hold is placed.
UCI IRB approval is also required prior to initiation of any drug study. Investigators interested in studying an investigational drug or biological product are required to complete additional information when completing the IRB application or when requesting an amendment to an IRB-approved study through Kuali Research (KR) Protocols. Investigators are asked to include the drug name, IND number and the date of IND submission. Frequently, investigators submit protocols to the IRB for review during the 30-day waiting period. If the IRB finds the protocol acceptable, approval is issued after documentation of a valid IND number from the FDA is provided to the UCI IRB. If the UCI investigator holds the IND, a copy of FDA IND application is required prior to IRB review.
Investigational Use of Marketed Drugs or Biologics
The investigational use of approved, marketed drug or biologic requires consideration of whether an IND is required. When the principal intent of the investigational use of a test article (drug, biologic or medical device) is to develop information about the product's safety or efficacy, submission of an IND or IDE may be required. Investigators interested in studying the above are also required to address additional information in Kuali Research (KR) Protocols when completing the IRB application or when requesting an amendment to an IRB-approved study.
- Most studies performed by researchers at academic institutions are exempt from IND requirements for certain investigations conducted with drugs already approved for marketing.
- The exemption applies where safety is not an issue (because of a similarity in dose, route of administration, and patient population with the approved labeling) and where the investigation is not being conducted for the purpose of changing the drug labeling (for example, where the study is not for purposes of adding a new indication or comparative safety claim).
- The FDA expects that the exemption criteria will apply primarily to researchers in academic or other institutions.
- The exemption is intended to reduce burdens on researchers while permitting FDA resources to be devoted to monitoring clinical investigations requiring FDA oversight and to reviewing marketing applications.
- Although exempt from most IND requirements, the investigations would nonetheless be subject to the general prohibition against promotion of investigational drugs, and to the other regulations designed to protect the rights and safety of patients, such as the IRB review and informed consent regulations.
- The IRB makes the final determination as to whether an IND or IDE application is required before the study may proceed.
According to FDA regulations the clinical investigation of a marketed drug or biologic does not require submission of an IND if all six of the following conditions are met:
- it is not intended to be reported to FDA in support of a new indication for use or to support any other significant change in the labeling for the drug;
- it is not intended to support a significant change in the advertising for the product;
- it does not involve a route of administration or dosage level, use in a subject population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product;
- it is conducted in compliance with the requirements for IRB review and informed consent;
- it is conducted in compliance with the requirements concerning the promotion and sale of drugs; and
- it does not intend to invoke a waiver of informed consent for emergency research
Control of Investigational Drugs or Biologics
Research involving the use of investigational test articles (i.e., investigational drugs or biologics ) requires that the Investigator or other appropriate individual or entity (e.g., hospital pharmacy), provide appropriate control of test articles.
Note: An Investigational Drug/Biologic Accountability Log must be maintained, if the study includes an investigational drug or biologic.
UCIMC Dispensing Policies and Regulations for Investigational Drugs and Biologics
UCIMC and its satellite clinics have their own policies regarding the administration of investigational drugs and biologics in order to assure patient safety and comply with JCAHO standards, California law, and California Department of Health Services regulations. Investigators conducting research in clinical settings should consult with the hospital pharmacy for guidance on UCIMC hospital policies. Consultation should take place before preparing the budget for the clinical study.
For more information, refer to the following UC Irvine HealthSystems Policies:
- Medication Management: Administration of Investigational Medications
- Control of Investigational Devices
UCIMC Investigational Drug Services:
|Investigational Drug Services||(714) 456-5905
|Inpatient Pharmacy Services|
• Sterile Products
|Chao Family Cancer Center Pharmacy||(714) 456-5324|
|Drug Information Service||(714) 456-6988|
|General Pharmacy Administration||(714) 456-5514|
Lead Researcher (Investigator) Responsibilities
Investigators conducting studies in which an investigational drug/biologic will be used must ensure adequate control of the drug or biologic. Adequate control and handling of investigational drug/biologic include all of the following:
- The investigator should ensure that the investigational drug/biologic is used only in accordance with the UCI IRB approved protocol.
- An investigator must administer the investigational drug/biologic only to participants under the investigator’s direct personal supervision or under the supervision of a sub-investigator directly responsible to the investigator.
- The investigator must not supply the investigational drug/biologic to any person not authorized to receive it.
- An investigator is required to maintain adequate records of the disposition of the investigational drug/biologic, including dates of dispensing, quantity currently maintained for dispensing, and amount of the investigational product dispensed to participants (a sample Drug/Biologic Accountability Log is available).
- If the investigation is terminated, suspended, discontinued, or completed, the investigator must return any unused supplies of the investigational drug/biologic to the study sponsor, or otherwise provide for disposition of the unused supplies as directed by the sponsor.
- If the investigational drug is subject to the Controlled Substances Act, the investigator must take adequate precautions, to prevent theft or diversion of the substance into illegal channels of distribution. These precautions include: storage of the investigational drug in a securely locked, substantially constructed cabinet or other securely locked, substantially constructed enclosure to which access is limited.
- Drugs: FDA: 21 CFR 312