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No. 4: May 31-June 4, 2010

Does Study of Botanical Product Require an IND?

Scenario:

Dr. Pedersen presents an investigator-initiated study protocol to the regulatory assistance staff in the Office of Clinical Research at his medical college. The protocol, as presented, is titled, “The use of Adirondack black raspberry juice for the treatment of Type II diabetes mellitus.” The regulatory staff immediately states that, based on the title, this is a drug study. Dr. Pedersen insists that black raspberry juice is a dietary supplement and therefore no Investigational New Drug (IND) application is needed. The regulatory director calls the Food and Drug Administration's (FDA) Botanical Review Team (BRT) and speaks with a medical officer in the Center for Drug Evaluation and Research (CDER) who deals with botanical products.

Solution:

After reading the protocol the medical officer makes several suggestions. These include changing the title to “The use of Adirondack black raspberry juice to maintain normal blood sugar levels;” changing the subject population to patients who are not yet diagnosed with Type II diabetics; and adding additional tests to assure patient safety. The medical officer says the use of Adirondack black raspberry juice is not to treat diabetes (a drug claim) but to maintain normal blood sugar levels (a dietary supplement claim). The protocol was submitted to the IRB and approved. The study was completed with no adverse events.

Lesson Learned:

Several months after the study was completed the regulatory director attends a conference and discusses this study with an FDA medical officer who is not directly involved in botanical products. This medical officer says that the intent of the researcher is to treat Type II diabetes with the juice. The changes made to the protocol do not alter the intent. He said an IND should have been submitted. The regulatory assistance staff now submits IND applications for all similar protocols. Some of the IND applications have been put into effect, while others have been exempted from the IND requirements. Sometimes it is better to error on the side of safety and let the FDA make the determination of IND applicability.

Pertinent Regulations and Documents:

The Food, Drug and Cosmetic Act defines drugs and dietary supplements (21 USC 321). The Code of Federal Regulations presents the criteria for IND applicability (21 CFR 312.2). The CDER Botanical Review Team (BRT) provides scientific expertise on botanical issues to the reviewing staff and ensures consistent interpretation of the Guidance for Industry-Botanical Drug Products. The following two FAQs are taken from the FDA’s Web site:

1. Are Investigational New Drug (IND) applications required for clinical studies of botanical products that are also lawfully marketed as dietary supplements?

Yes. If a lawfully marketed botanical dietary supplement is studied for its effects on diseases in the proposed investigation (i.e., to cure, treat, mitigate, prevent, or diagnose disease, including its associated symptoms), then it is an investigational new drug and will be subject to IND requirements. This applies to studies in INDs sponsored for both commercial and academic research purposes.

2. Are INDs required for studies evaluating the uses of botanical dietary supplement as dietary supplements?

No. When a lawfully marketed botanical dietary supplement is studied for its dietary supplement use (i.e., structure and/or function claims), an IND is not required. Structure and function claims are statements that describe the effect a dietary supplement may have on the structure or function of the human body.

Comments by Harvey M. Arbit, PharmD, MBA, president of Arbit Consulting, LLC. He specializes in FDA regulatory affairs related to investigator-initiated IND and IDE research.