NPA filed the comments this week, responding to a request FDA put out in December on a proposed rule change for the definition of the term ‘Biological Product.’ While the rule applies mostly the regulation of vaccines and so forth, it could have implications for supplements and foods, said NPA president and CEO Dan Fabricant, PhD.
The new proposed rule defines a protein as a molecule consisting of more than 40 amino acids. The thinking is that if it contains fewer amino acids, the resulting molecule will be too small to exhibit the functional groups that give proteins their biological activity, whether as an enzyme, as part of a signaling pathway or what have you.
The new proposed rule also defines a 'chemically synthesized polypeptide' as any alpha amino acid polymer made entirely by chemical synthesis and greater than 40 amino acids but less than 100 amino acids in size. The goal of the new rule is to clarify the regulation of these substances.
Length less important than monomeric or oligomeric nature of proteins
But in its comments, NPA said there are examples of proteins in nature that are smaller than this. The agency relied on outdated information lifted from a textbook when taking this approach, NPA said.
“Scientific discoveries more recent than 2002 have showed proteins in existence less than 40 amino acid residues long. Furthermore, amino acid polymers do not need 40 amino acids to assume secondary and tertiary structural conformations indicative of proteins,” NPA’s comment states.
“It appears the sequence length a protein needs in order to fold up into secondary and tertiary structures and activate transmembrane bound receptors is typically on the order of 30 amino acids in humans from the evidence available to date. However, the rest of the animal kingdom has devised ways for even smaller numbers of amino acid residues to act and function as proteins,” the comment added.
NPA’s comments go on to stress that the dentition of what’s a protein and what isn’t should take into account the notion that proteins can be monomeric (consisting of one peptide) or oligomeric (two peptides up to many thousands), and those individual peptides might fall below the 40 amino acid limit. For example, one important protein mentioned in the proposed rule—insulin—consists of two peptides, one 21 amino acids long, the other consisting of 32 amino acids.
Fabricant said the new rule is similar in some ways to the FDA’s effort in which it sought to define which isolated fiber ingredients met the definition of dietary fiber and which didn’t.
“Where is the public safety concern here?” Fabricant said to NutraIngredients-USA. “This is a rule that could potentially affect our commodities in this business. This is similar to the fiber rule in that it could have unintended consequences.”
Fabricant said the proposed definitions of a polypeptide being less than 100 amino acids long, and a protein being greater than 40 will further muddy the waters rather than clarifying the issue.
“Polypeptide and protein should not be defined as a continuum of amino acid length. Stated another way, proteins are always polypeptides (or composed of one or more polypeptides as subunits in a greater complex) but not all polypeptides are proteins. A polypeptide can be a protein if it does not need any other polypeptide subunits to function,” NPA’s comment states.