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May 31

No. 4: Does Study of Botanical Product Require an IND?

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No. 4: May 31-June 4, 2010

Does Study of Botanical Product Require an IND?


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.


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.

Comments (8)
written by Sam, May 27, 2010
The regulatory staff are correct here. A nutritional supplement used in the treatment of a disease is no longer a supplement, but a drug. No nutritional supplement would have in the label a claim that it can be used to treat an illness. Dr. Pederson can check.
Assistant Professor, Dept of Psychiatry MUSC
written by Jennifer Donovan, June 02, 2010
The regulatory staff are correct in that and IND will be needed. I do wonder, however, as obesity is indeed a disease, when an IND will be required for using specific foods or beverages to "treat obesity". Do I need an IND if I wanted to do a study where patients replaced their daily soda with a whole fruit and a glass of water? In otherwords, when will I need to get an IND for an apple?
written by BR, June 02, 2010
Interesting comments. When does a disease start and "structure and function" variance end?
Scenior Scientist
written by MSJ, June 02, 2010
"Intent"? How did intent slip in here? A protocol is an objective procedure that stands on it's own. There's no call to bring in the intent of the researcher. Obviously the specifics of the studied population determine its generalizability, but that is another matter.
written by Dr. Arbit, June 02, 2010
Answer to BR's question. In FDA's guidance on implementation of "Qualified Health Claims" states: Structure/function claims describe the effect that a substance has on the structure or function of the body and do not make reference to a disease. An example of a structure/function claim is "Calcium builds strong bones." Health claims characterize a relationship between a substance (specific food or food component) and a disease or health-related condition. An example of a health claim is "Diets low in saturated fat and cholesterol that include 25 grams of soy protein a day may reduce the risk of heart disease".
written by Dr. Arbit, June 02, 2010
Response to Jennifer Donovan. Keep in mind there is a difference between medical practice and clinical research. The FDA does not regulate medical practice. Prescribe whatever foods you believe are in the best interest of the patient to treat obesity. If you plan to conduct clinical research to answer a hypothesis that apples "treat" the disease obesity the FDA may say that is not a drug. However if you substitute some article other than a food and you claim that the article is "intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals" the FDA may in fact determine that to be a drug and require an IND to conduct the research. I always recommend contacting the FDA in these cases. Often times the answer you receive is dependent on the medical reviewer. (http://www.fda.gov/RegulatoryI...086297.htm)
written by JEC, June 03, 2010
It seems that had the British Navy sought to study the use of limes to prevent and/or cure scurvy aboard ships under present day US FDA regulations, they would have been required to obtain an IND. While this makes sense at one level (to protect the safety of the sailors) it seems absolutely silly at another (limes were commonly eaten in several parts of the world at the time). Food can prevent/treat illness. How does this make it a drug?
written by Dr. Arbit, June 09, 2010
Response to JEC. If the limes in the grocery store are labeled for the prevention of scurvy they are drugs. If you conduct a clinical research study to prove scientifically that limes prevent scurvy the limes are drugs in that study. Otherwise the lime you place in your ice tea is simply a fruit.

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