If your study involves a test drug and a medical outcome (i.e. something to prevent, diagnose, or treat disease), the FDA requires an Investigational New Drug (IND) application before your product can be studied in a clinical trial. This application presents evidence to the FDA that your product is relatively safe for use on human subjects and is reasonably expected to offer a benefit.
This is accomplished through a comprehensive and lengthy application which compiles all of the existing evidence on the ingredients, including laboratory tests, animal testing, manufacturing procedures, and history of human use. The IND also requires a proposed research study so that the FDA can confirm its suitability.
The IND is more than a formality; it is a violation of the FDA's Food, Drug, and Cosmetic Act to ship an unapproved drug in interstate commerce (21 U.S.C. § 355(a)). The IND provides authorization test the unapproved new drug in human patients through participating medical centers for the purpose of evaluating the product's safety or efficacy.
Not all products require an IND for clinical research. Natural products, unlike regular drugs, are typically designed to enhance the structure or function of the human body. If this is the case, a clinical trial is still required to substantiate product claims, but the trial can be conducted without an IND.
The key factor here is not the product or formulation; it's the outcome. For drug effects, INDs are required; for health promoting effects, INDs are not required.
The IND Includes:
Introduction: "This section is intended to place the clinical development plan for the Investigational New Drug into perspective and to help FDA anticipate the needs of the future program." - FDA
CMC (Chemistry, Manufacturing, & Controls): These are among the "non-clinical components" of the application. This section includes details on the physical, chemical, or biological characteristics of the ingredients; flow diagram of the general method of preparation of the product; overview of testing to ensure purity, strength, and quality; details on product storage and shelf life; placebo formulation for the proposed clinical study, proposed labeling of products for research purposes; and an environmental assessment. Most of this information is supplied by the manufacturer; our team can provide support for the collection and organization of this information.
PT (Pharmacology & Toxicology): This is the second group of "non-clinical components" for the application. This section includes findings from laboratory and/or animal studies on the safety of the product. Sufficient evidence must be included in this section to demonstrate that the product is safe for use in human studies. For the vast majority of botanical products and dietary supplements, this information does not require new research; it can be sourced from the existing body of scientific literature. Pharmacokinetic data on the proposed mechanism of action of the product are also included in this section.
Clinical Protocol: This begins the "clinical components" part of the application. Detailed protocols for each clinical trial proposed must be provided to the FDA for review. This includes inclusion/exclusion criteria, sample size justification, outcome measurement validation, adverse event collection & reporting, statistical analysis plans, and other relevant study details. This should be compiled by the research team which will be conducting the proposed studies.
Investigator's Brochure: The Investigator's Brochure provides a description of the substance, summarizes all of the pharmacological & toxicological effects in humans (or animals if human effects are not yet known), summarizes the pharmacokinetics and biological disposition of the product, provides an overview of safety and efficacy from prior studies, where available, and describes the possible risks and side effects of the product (with patient monitoring instructions). This is also compiled by the research team.
Investigator's Statement: This statement confirms the primary investigator's qualifications, experience, and ethical authorization. It also confirms that the investigator will conduct the studies according to the IND authorization and other legal/ethical requirements. This can only be completed by the primary investigator.
Human Experience: This section details all prior human experience, including marketing and sales of the product globally, prior clinical trials or other human studies, and other data which may substantiate that the product is safe for human use. Most botanical products have extensive human experience that is outlined in this section.
Additional Information: The FDA may require additional information, such as addiction potential of the substance(s), plans for pediatric studies, etc. This is determined on a case-by-case basis, depending on the proposed substance and target population.
A complete IND is a lengthy document, which requires interdisciplinary expertise. Incomplete INDs can result in costly delays to the research process, lengthening the timeline between development and drug approval. Our team of experts can compile portions of the IND or the entire IND application for your proposed studies, depending on your company's needs.