Extractables/Leachables

With an ever-increasing consumption of pharmaceutical products by the world population, there are considerable concerns about the unknowns and impurities which are ingested along with these medicinal drugs. The nature of these impurities and their consequent effect may pose a potential hazard to human health. This makes identification, estimation, quantification and control of these impurities matter of great concern and challenge. Regulatory agencies are laying increasingly defined guidelines for different types of impurities both for drug substances and drug products. Chemical properties of these impurities are diverse. Accordingly laboratories need to use variety of analytical equipment like LC-MS/MS, UHPLC, GC-MS, GC-MS/MS, ICP-MS. Shimadzu has been a trusted scientific partner for these analytical equipment, with workflows suitable for impurity analysis and compliance platforms tailor-made for the pharmaceutical business environment. In this handbook, we share a variety of methodologies for different classes of impurities like elemental, organic, residual solvent and more. Methods described are in synchronization with relevant ICH guidelines and create a sound platform for scientists to initiate their quest for answers with confidence.

THS can be used for measurement of thermal extracts from pharmaceutical packaging, the same as TD. In comparison with TD and other concentration systems, high sensitivity measurements can be performed inexpensively and with quick extraction. Since the system can switch between trap mode and loop mode, rather than being a dedicated E&L system, it can be utilized for a wide range of applications including the analysis of residual solvents, impurities, and diffused gases

Mutual interactions between the pharmaceutical and packaging are a problem with pharmaceutical packaging materials that requires particular care. Extractables are compounds generated from storage conditions that are more severe than normal, whereas leachables are compounds that can be transferred from the packaging to the pharmaceutical under normal storage conditions. They are classified as indicated in Table 1. Before pharmaceuticals can be sold, extractables and leachables must be comprehensively verified to determine packaging material risks.

Extractables are defined as the compounds that can be extracted from a drug packaging under certain conditions, e.g. in solvent and/or with heating. Meanwhile, leachables are compounds that migrate from the drug packaging into the drug under normal storage conditions. Many regulatory guidance documents have been established regarding extractables and leachables (E&L) approach and assessment. However, details on how to perform E&L evaluation in various packaging materials and products is still under discussion and development. A screening analysis method for extractables in the packaging of ophthalmic solution by thermal desorption (TD) - GCMS was developed in this study. The result is compared with the leachables result of an ophthalmic solution measured by GCMS with liquid injection.

Since food contact materials (FCMs) are in direct contact in consumer products, the existence of extractables and leachables (E&L) in the packaging and storage materials can raise health and safety concerns. To address these concerns and comply with the regulations, companies demand methods and techniques to analyze their products for research and development as well as quality assurance purposes. In response to this increasing demand, we developed a method to analyze extractables and leachables in FCMs using a liquid chromatography high accuracy mass spectrometer.

Plastic packaging systems for pharmaceutical products must be suitable for their intended use. The US Pharmacopeia revised the related chapter. It is published in USP 39- NF34, which will be valid from May 2016. Besides the change of the title “Plastic Packaging Systems and their Materials of Construction”, two new chapters are established. This application note is related to the first chapter 661.1.

In the pharmaceutical industry plastic packaging is used in various forms for example for intravenous bags, bottles, cartridges or pre-filled syringes. The packaging must be tested for suitability for these uses. It is published in USP 39-NF34, which will be valid from May 2016. Besides the change of the title "Plastic Packaging Systems and their materials of Construction", two new chapters are established. This application note is related to the second chapter 661.2.