Bass, 1995). If the ingredient is “new,” the manufacturer must notify FDA 75 days in advance of introducing it or a dietary supplement containing it into commerce (DSHEA, P.L. 103–417, § 8, 108 Stat. 4331 (1994)]. If FDA disagrees with a manufacturer’s determination of new when a manufacturer sells an ingredient without giving the 75-day notification to the agency, the government bears the burden of proof to show that the substance is a new dietary ingredient requiring such a submission and that the product containing it is therefore adulterated.
It is important to note that the 75-day notification period applies to new dietary ingredients, but not new products. A product that is a new combination of ingredients marketed prior to October 1994 does not require submission of a 75-day notification.
Although less relevant to this report, DSHEA also provided for a government commission to consider the marketing and labeling of dietary supplements. The findings of this commission are described in the Report of the Commission on Dietary Supplement Labels (CDSL, 1997), which addressed health claims, nutritional support statements, substantiation files for claims and safety, and publications used in conjunction with sales.
Since a dietary supplement manufacturer is generally not required to share its basis for safety determinations with FDA before marketing, FDA determines possible safety issues from publicly available information it collects and from data that it generates in its own laboratories. In some cases, FDA may not be able to gather enough data to be confident about the safety of a particular product; without demonstrating that a substance does not meet the standard of safety—representing a reasonable certainty of no harm—FDA has no authority to remove it from the marketplace. FDA has acted when aware of possible harmful effects with various levels of response: it may warn consumers as it did in 2001 with comfrey and lipokinetix; it may warn health care practitioners that a supplement may be a serious health risk and ask them to review and report cases of adverse effects as it did with lipokinetix and with kava in 2001; or it may request a voluntary recall by manufacturers and distributors as it did with aristolochic acid in 2001. In the case of ephedrine alkaloids in 2003, for the first time FDA issued a warning letter to the manufacturer or distributor of a dietary supplement ingredient indicating that it intended to take action to remove a product; this was incorporated into a final rule in 2004 (21 C.F.R. § 119). Recently, manufacturers of androstenedione were noti-