Establishing Extractables Testing from Plastic Packaging Materials and Systems for Pharmaceutical Use by TOC Analysis According to USP Application Note · multi N/C pharma

Introduction

The USP chapter <661> (formerly known as “Container-Plastics”) was revised under the title “Plastic Packaging Systems and their Materials of Construction”. The two new sub chapters of the new monograph describe TOC testing approaches of water-based extracts addressing “Plastic Materials of Construction” <USP 661.1> and “Plastic Packaging Systems for Pharmaceutical Use” <USP 661.2>.

The whole chapter aims at further improving product safety of pharmaceutical products by using only well-characterized materials for packaging. Besides TOC testing these materials and systems should be characterized with regard to their identity, biocompatibility (biological reactivity), physicochemical properties (like UV/Vis absorbance, alkalinity or acidity), plastic additives and extractable metals.

According to USP <661.1> and <661.2> the TOC methods used need to provide a linear dynamic range of 0.2–20 mg/l TOC with a detection limit of max. 0.2 mg/l. The TOC limit value in plastic materials of construction used in packaging systems is NMT (not more than) 5 mg/l (USP 661.1) and in plastic packaging systems for pharmaceutical use it is NMT 8 mg/l (USP 661.2).

For the analysis, purified water extractions from polymer packaging materials have to be prepared under described conditions and to be tested for TOC within four hours after preparation according to USP <643>. USP <643> represents the general method for TOC testing in pharmaceutical applications and provides guidance on how to qualify the analytical technique for use as well as guidance on how to interpret instrument results for use as a limit test (e.g. the 500 ppb limit for WFI – water for injection).

This application note describes the procedure for TOC analysis according to USP <661.1> and <661.2> on the TOC analyzers of the multi N/C pharma series the multi N/C pharma UV, the multi N/C pharma HT and the multi N/C 3100 pharma and proves their outstanding performance for these test methods.