The regulatory history of parenteral nutrition lipid emulsions in the US has been reviewed by use of publicly available US government databases. The technical basis for current regulatory policy was explored through analysis of the Food, Drug & Cosmetic Act, and the Code of Federal Regulations, as well as the transcript of an FDA public workshop. Position papers published by professional associations and review articles published by nutrition experts were also examined.
Significant challenges now face FDA as it seeks to decide approval criteria for NDAs for lipid emulsion parenteral nutrition products, as products containing new kinds of lipids are submitted for approval for the first time in 29 years.
"Several lipid emulsion products for parenteral nutrition were approved by FDA between 1975-1984, derived from either soybeans or a mixture of safflower oil and soybeans. No new kinds of lipid emulsion products have been approved in the US since 1984, although some new versions and concentrations of products already on the market were approved between 1984-1998. At the present time, only one lipid emulsion is on the market in the US, a product derived from soybeans. Recently, changes in the demands for these lipid emulsions have caused them to be added to the FDA’s list of drug shortages in the US.Newer lipid emulsion products, derived from a variety of lipid sources, have been available in most other countries for many years. FDA is now reviewing applications for developing such products for use in the US and is finding challenges in doing so, as reflected by the scheduling of an FDA Advisory Committee on parenteral nutrition lipid emulsions for October 2012 that was subsequently cancelled.
Patients who are unable to obtain adequate nutrition by eating or by the enteral route must receive it intravenously (as parenteral nutrition) in order to survive; lipid emulsions are usually an important part of these parenteral nutrition regimens. The standards for approval of new drugs have advanced greatly during the 29 years since the last approval of a new kind of lipid emulsion product in the US. However, many of the requirements are not easily applied to products with nutritional indications. Although parenteral nutrition lipid emulsions are regulated as “drugs” under the definitions in the Food, Drug and Cosmetic Act and Code of Federal Regulations, in many of their characteristics and medical uses they are more like foods than like drugs. A major similarity to foods is that their purpose is to provide essential fatty acids needed to maintain the structure of cells and tissues during a period when patients cannot eat, to provide energy, and in children, to provide the substrate for growth. A major difference from foods is that they are given intravenously. The medical need to approve new lipid emulsions appears to call for a new regulatory paradigm for parenteral nutritional products. A meaningful basis for approval would be requiring clear evidence of safety, and evidence of efficacy based on nutritional equivalence to previously approved products. Continuing discussion by regulatory specialists will be needed in order to determine how to get new lipid emulsions to US patients who need parenteral nutrition in order to survive.