March 2, 2009 – The Food and Drug Administration (FDA) recently announced its conclusion that pyridoxamine does not meet the statutory definition of a dietary supplement. While pyridoxamine is a vitamin, this decision has relevance for the herbal industry because FDA’s decision is based in part on the agency’s conclusion that the trade associations’ lists of “grandfathered” ingredients are inadequate to establish either that an ingredient was marketed prior to Oct. 15, 1994 or that it was marketed prior to the approval of an investigational new drug application (IND).
“The American Herbal Products Association is disappointed with the FDA’s dismissal of the ingredient lists compiled by industry,” said AHPA President Michael McGuffin. “However, they still have legitimate value, and we encourage companies to gather evidence of when dietary ingredients identified in the lists were first marketed.”
The Federal Food, Drug & Cosmetic Act (FFDCA), as amended by the Dietary Supplement Health and Education Act of 1994 (DSHEA), exempts dietary ingredients marketed prior to Oct. 15, 1994 from the pre-market notification requirements for new dietary ingredients (NDI). The FFDCA also allows dietary ingredients marketed prior to authorization for investigation as a new drug “for which substantial clinical investigations have been instituted and for which the existence of such investigations has been public” to remain in commerce.
Following passage of DSHEA, companies and individuals submitted the names of dietary ingredients marketed as dietary supplements or foods prior to Oct. 15, 1994 to industry trade groups. The trade groups, including AHPA, used this data to compile lists of “grandfathered” or “old” dietary ingredients that were then submitted to FDA.
“Vitamin B6 comprises three chemically, metabolically, and functionally related forms – pyridoxine (pyridoxol, PN) pyridoxal (PL), and pyridoxamine (PM).” Food and Nutrition Board, National Research Council, Recommended Dietary Allowances (10th Ed. 1989) p. 142. While pyridoxamine was a known form of Vitamin B6, the issue with respect to DSHEA is whether the ingredient was marketed as a dietary supplement or as a food pre-DSHEA.
In 2005, a citizen petition was filed on behalf of Biostratum Inc., the manufacturer of the investigational new drug Pyridorin (pyridoxamine dihydrochloride), to request FDA determine the regulatory status of pyridoxamine. FDA issued a Federal Register notice inviting comment on the petition. In comments supporting pyridoxamine as a “grandfathered” ingredient, the Council for Responsible Nutrition (CRN) submitted to FDA an ODI list compiled primarily by the Natural Products Association (then NNFA) that listed pyridoxamine as a dietary ingredient on the market before the passage of DSHEA.
In a letter to Biostratum counsel dated Jan. 12, 2009, FDA announces its decision that pyridoxamine is not a dietary supplement and asserts, “The fact that pyridoxamine appears on an industry-generated list of allegedly grandfathered dietary ingredients does not constitute evidence sufficient to establish that pyridoxamine was marketed as a dietary supplement before it was authorized for investigation as a new drug” in 1999.
According to FDA, the list is inadequate because it does not provide “independent, verifiable evidence” of prior marketing. Namely, the trade groups did not trade groups did not include any marketing data, such as product labels or catalogs, that establish that pyridoxamine was marketed as a dietary supplement or as a food pre-DSHEA. The mere listing of the ingredients on the trade group lists was not enough.
AHPA has a list of grandfathered ingredients and, in an effort to gather such supporting data for this list, the association urges members to submit to AHPA pre-1994 product catalogs, labels, ad material and business records that provide substantiation a dietary ingredient was either offered for sale in the U.S. as a dietary supplement or food or was marketed as a component of a product offered for sale in the U.S. as a dietary supplement or food. The following chart provides more information on FDA’s current thinking regarding the substantiation that a product meets the dietary supplement definition under DHSEA’s prior-marketing clause.
Source: American Herbal Products Association, www.ahpa.org