FDA Updates Bulk Drug Substances List with Amino Acid Solutions

March 4, 2019

On March 1, the U.S. Food and Drug Administration announced updates to the categories of bulk drug substances under its interim policy under section 503B of the Federal Food, Drug, and Cosmetic Act. As previously reported, SNMMI sent a petition to FDA last year requesting arginine and lysine be added to 503B bulks list or moved to the 503B Category 1 list.

SNMMI became aware of the issue through member feedback and subsequently sent recommendations to FDA. Specifically, SNMMI recommended that the FDA consider placing arginine and lysine on the 503B bulks list so that the outsourcing facilities can start using these two amino acids in compounding the amino acid solution for lutetium-177 dotatate (Lutathera®) treatment.

According to the package insert, an amino acid solution is to be administered to patients 30 minutes before and during the administration of lutetium-177 dotatate. To protect patients from potential renal toxicity, the amino acids arginine and lysine are recommended. Unfortunately, a solution containing only those amino acids is not commercially available; they are only offered in combination with other amino acids and substances that can cause patients significant discomfort, especially nausea and vomiting.

SNMMI commends the FDA for their swift action to update the 503B Bulk Drugs list, which will ultimately make it easier for manufacturers to compound and make available an arginine/lysine only solution. This will help patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to tolerate and, therefore, benefit from lutetium-177 dotatate therapy.

Additions to the 503B Bulk Drugs Category 1 list:

  • Arginine hydrochloride
  • L-arginine hydrochloride
  • L-lysine hydrochloride
  • Lysine hydrochloride

For more information please see the Federal Register Notice issued on March 1, 2019.