Extractables and Leachables Testing Using a Quality Risk Management Approach

Presented by Dhaval Tapiawala, Principal Scientist at Pfizer • Understanding extractables and leachables for better adoption of single use systems • Ensuring safety of drug through determining the level of leachables throughout product life cycle • Case Study of implementation of standardized testing protocol and followed by Large Volume Parenterals (LVPs): Extractables/Leachables: Challenges when executing an E/L Program A traditional chemical characterization approach for qualifying Large Volume Parenteral Container/Closure systems from an Extractable/Leachable perspective becomes challenging due to the defining characteristics of this dosage form. The large daily volumes of drug product administered to a patient – volumes which could be as high as a few liters per day – drive the AET down to levels that are analytically challenging, if not impossible to meet. Moreover, the composition of LVP drug products can be sufficiently complex that response interferences are exacerbated.  Thus, the analytical assessment of E/L compounds in LVPs, including discovery, identification and quantitation, will need to be performed at much lower concentration levels, both in the extracts (in extractable studies) as well as in the drug product (leachable studies). This circumstance has implications on the design of the study, the analytical instrumentation and methods used, the processes used to secure the required information, and the subsequent toxicological risk assessment of the discovered, identified and quantified leachables. This presentation will give a helicopter view on all problems one can encounter in a LVP-qualification process, and will then take a deeper dive into how simulation studies for LVP could assist in addressing some of the issues in the study design and subsequent steps of the qualification process. Presented by Dr. Dennis Jenke, Principal Consultant for Nelson Labs