Fatty Acid Extractables/Leachables Profiles as an Indicator of Technical Grade Stearate Acid Additive Origin

Medium-chain fatty acids are used extensively as additives to plastics and elastomers. Plastics and elastomers are in turn used in the fabrication of components which then are used in the fabrication of drug product container closure-delivery systems and medical devices. As a result, these medium-chain fatty acids routinely appear in extractables profiles from these components as well as in leachables profiles of drug products. The most commonly used medium-chain fatty acid additive is “Technical Grade Stearic Acid” either as the free base or salt (e.g., Mg, Ca, Zn). Technical Grade Stearic Acid contains a mixture of fatty acids, with Palmitic (C16) and Stearic (C18) acids being the most abundant. These fatty acid mixtures are of biological origin, either plant or animal derived (bovine). It is well established in the scientific literature that the ratios of C16/C18 in fatty acid mixtures vary with origin.

This presentation focuses on the use of extractables and leachables profiles to indicate the origins of fatty acid additives in packaging and medical device components. Data will be presented from both GC/MS and LC/MS analyses of various extractables/leachables profiles and compared with the chromatographic profiles of fatty acid mixtures of known origin. It will be shown that plant and animal derived C16/C18 ratios can be distinguished by either analytical technique, alerting the analytical chemist to the possibility of a bovine sourced additive with the potential of carrying Bovine Spongiform Encephalopathy (BSE).

Presented by Daniel Norwood, Principal Consultant at Feinberg Norwood & Associates Pharma Consulting

Dr. Daniel Norwood joined SCIO Analytical as Executive Partner in June 2015. In 2019, SCIO Analytical became Feinberg Norwood & Associates Pharma Consulting and Dr. Norwood was named Principal Consultant. Prior to SCIO Analytical, Dr. Norwood was a key technical employee at Boehringer Ingelheim Pharmaceuticals where he was successful in various pharmaceutical development roles, including Director Physical and Chemical Analysis. In June 2015, Dr. Norwood retired with the title of Distinguished Research Fellow in Analytical Development. Dr. Norwood is an internationally recognized expert in the field of leachables and extractables assessment in pharmaceutical development and manufacturing. He served as chair of the widely-quoted Product Quality Research Institute (PQRI) Working Group on leachables and extractables in inhalation drug products. He is also a member of the PQRI Working Group on leachables and extractables in parenteral and ophthalmic drug products (PODP) and has served on various technical teams of the International Pharmaceutical Aerosol Consortium on Regulations and Science (IPAC-RS). From 2010-2020, he served as a member of the USP Expert Committee on Packaging and Distribution where he has chaired the subcommittee on extractables and leachables. Dr. Norwood has received several industry awards, including the CEO’s Award from Glaxo (1994), the President’s Award from Boehringer Ingelheim (2007), the Excellence in Research Award from PQRI (2009), and the Award for an Innovative Response to Public Health Challenges from USP (2013).