Notice Number: NOT-AT-05-003 (See also, NOT-AT-05-004)

Update: The following update relating to this announcement has been issued:

• August 16, 2010 - See Notice NOT-AT-10-006 This Notice is to inform the research community that NCCAM has updated its Policy and Guidance on Product Integrity of agents used in NCCAM funded research.

Key Dates
Release Date: April 29, 2005

I. Definition

Biologically active agents are defined (for this policy) as those test agents derived from biological sources or small biologically active molecules used as complementary and alternative therapies. These represent a highly diverse group of substances that include, but are not limited to, products derived from botanicals or animals, vitamins, minerals, fatty acids, amino acids, proteins, small molecules such as SAMe and creatine, as well as pre- and probiotics, and functional foods. Functional foods are defined as unmodified and modified foods, consumed as part of the usual diet, that may have physiological benefits and/or reduce the risk of disease beyond basic nutritional functions.

For purposes of this policy, the definition of biologically active agents does not include animals (e.g., maggots or helminthes), test articles considered by the U.S. Food and Drug Administration (FDA) to be devices (e.g., leeches), or drugs.

Note: Although homeopathic medicines can be included in this definition of biologically active agents, they are currently not included in this policy document.

II. Policy

In pursuit of its mission, NCCAM will support research investigating the safety, efficacy, pharmacokinetics, pharmacodynamics, bioavailability, identification of active constituents and biomarkers, and mechanisms of action of biologically active agents used in complementary and alternative medicine (CAM).

A. Product Quality

1. Investigators must provide evidence to convince NCCAM that the biologically active test agents and their placebos proposed for investigation are of sufficient quality to ensure that investigations can be reproduced. (See NOT-AT-05-004: NCCAM Interim Applicant Guidance: Product Quality ) This policy will be effective starting with the June 1, 2005, application receipt date.

2. Investigators must reserve test agent and placebo samples from each batch for verification at later dates of product quality, stability over time, and comparability from batch to batch. Before grant award, NCCAM will request that the applicant submit a plan for a sampling scheme, storing and analyzing samples, determining tolerable variances, and making the results of the analyses available to NCCAM. (See NOT-AT-05-004: NCCAM Interim Applicant Guidance: Product Quality ) NCCAM may request access to the resulting records of these analyses and even aliquots of study materials for independent analyses. Special terms of award will be added to the Notice of Grant Award pursuant to 42 CFR 52.9 and 45 CFR 74.53. These terms require that the grantee be responsible for implementing the proposed and NCCAM-evaluated plan and submitting the requested information to NCCAM. Lack of compliance with the terms may be grounds for termination of the award. This interim policy will be effective starting with the June 1, 2005, application receipt date.

B. Scope of Research

1. NCCAM will accept applications for studies testing the efficacy of biologically active agents only if the applicant provides justification for dose. The justification must include the results of dose-ranging studies. The efficacy study may be a dose-ranging study itself.

2. NCCAM supports investigation of complex natural products. It will support studies of isolated constituents from complex natural products when the intent is to: (a) characterize and standardize whole products (e.g., botanicals), (b) compare the actions of single constituents with the complex product from which they are derived, (c) identify mechanisms of action for the whole product, or (d) better understand or optimize the production of the whole product. NCCAM, however, will NOT support research on the isolation of single constituents for the sole purpose of developing these constituents as discrete drugs.

3. NCCAM will support investigation of essential nutrients, such as vitamins and minerals, in amounts that are pharmacological or at the very high levels recommended in the practice of orthomolecular medicine. NCCAM will not support study of nutrient deficiencies due to inadequate intake or known increased requirement secondary to disease processes.

4. NCCAM will accept applications to study synthetic or chemically pure products if they are already marketed in the U.S. and in public use as dietary supplements. NCCAM will accept applications to study synthetic variants of compounds derived from natural products if the purpose is to explore the mechanism(s) of action related to the natural product.

5. Investigators considering submission of application to study live animals used medicinally, such as maggots, helminthes and leeches, should contact an NCCAM Program Officer concerning NCCAM's willingness to accept the application.

C. IND Application

1. Investigators proposing clinical studies should contact the FDA to determine if the investigator must submit an Investigational New Drug (IND) application. (See Considerations for NCCAM Clinical Trial Grant Applications, http://nccam.nih.gov/research/policies/clinical-considerations.htm).

III. Contacting NCCAM

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