The United States Pharmacopoeia (USP) General Chapters - Packaging and Distribution Expert Committee has now proposed a new chapter to address the qualification of plastic components used in the manufacture of APIs (active pharmaceutical ingredients) and drug products (DPs). The suggested title of the new chapter 661.3 is Plastic Components and Systems Used in Pharmaceutical Manufacturing. The draft is open for comment until July 31, 2016.
The chapter is part of a suite of chapters, including plastic packaging systems and their materials of construction, plastic materials of construction, plastic packaging systems for pharmaceutical use and evaluation of plastic packaging and manufacturing systems and their materials of construction with respect to their user safety impact. In addition a section has been added to general chapter 1661 to support the use and understanding of the new general chapter 661.3.
In the Pharmacopoeial Forum (PF) 42(3) (May-June 2016) chapter 661.3 addresses the qualification of plastic components used in pharmaceutical manufacturing and is applicable solely to those processes that involve liquid process streams and process intermediates due to the expected increased degree of interaction with liquids. Plastic manufacturing systems for pharmaceutical use include bags, cassettes, chromatographic columns, connectors, filling needles, filters, sensors, tanks, tubing, and valves. Elastomeric parts such as diaphragms, gaskets, and O-rings are not in the scope of this chapter.
The manufacturer of APIs and DPs is responsible for ensuring that the plastic components and systems used are suited for the intended purpose. It is likely that raw materials, intermediates, process streams, APIs, and DPs will get in contact with one or more plastic components during the manufacturing process, result in process-related impurities (PrIs). Now these PrIs have the potential to alter a quality attribute of the DP, if it persists through the manufacturing process.
Plastic manufacturing components and systems are chemically suited for their intended use with respect to safety if they are constructed from well-characterized materials that have been intentionally chosen for use as established by the test methods included in general chapter 661.1, stated the draft.
The general physicochemical properties of the components have been established; The biocompatibility has been appropriately established using appropriate chemical testing, such as extractables or leachables profiling and toxicological assessment of the test data ‘chemical safety assessment’.
The chapter provides guidance on the appropriate application of biological reactivity tests. A two-stage approach consisting of an initial assessment followed by a risk assessment leads to the required level of component characterization. The initial assessment examines purpose and composition of component or system, composition of DPs, processing conditions and product dosage form.
The demonstration of equivalence would allow acceptance of the system without any further characterization. If equivalence cannot be established between the system then a Risk Assessment should be conducted. The outcome of this assessment results in three risk levels: low (A), moderate (B), and high (C). These levels are linked according to the risk of the individual dosage form for instance solid oral and liquid oral.