Agency expectations are quickly evolving for the evaluation of drug product packaging and delivery systems and the surfaces used during manufacture with respect to potential leachables. Every new and generic drug product must be assessed for extractables and leachables (E&L). In this top five list, Alcami experts will address the extractables and leachables questions our experts hear most.
- What is the difference between an extractable and a leachable?
Extractables are compounds that can be extracted from a packaging component, delivery system, or manufacturing surface via laboratory manipulation, such as exposure to solvents or heat. Extractables can be potential leachables. Leachables are compounds that passively migrate into the drug product over time, as a result of direct contact from the packaging system, in-use componentry, or a manufacturing surface.
- What types of studies does Alcami support?
Alcami’s most frequently performed study types are extractables evaluations of packaging components, leachables evaluations of aged drug product, and leachables evaluations of manufacturing surfaces. We also have experience with in-use studies for drug product delivery systems, simulation studies, and migration studies with respect to secondary packaging such as labels, inks, and dyes.
- When should an extractable and leachable study be performed?
The most common phase to perform an extractable and leachable screen of primary packaging is at the end of Phase II, while manufacturing studies are generally performed during Phase III. However, there is minimal risk in initiating these studies earlier, provided the packaging componentry or manufacturing train has been finalized. Additionally, Alcami can perform E&L studies in support of the component selection process.
- Which guidelines does Alcami use to determine study design?
Over the years, the US Pharmacopeia (USP), International Harmonisation (ICH), Product Quality Research Institute (PQRI), and several other industry consortia have developed guidelines and best practices for these E&L studies. The selection of which guideline(s) to follow is based on the component to be evaluated, drug product formulation, the route of administration, dosage regimen, and credibility with the applicable governing agency. The resulting study design will have a scientifically justified approach to sample handling, analysis, and reporting to help ensure regulatory compliance specifically tailored for the drug product-packaging system.
- What types of materials and drug products does Alcami have experience with?
Alcami has specialized knowledge of the most common materials of construction such as platinum-cured silicon, halobutyl rubber, cyclic olefins, polyethylene terephthalate (PET), polyvinyl chloride (PVC), and other elastomers. Vial and stopper configurations, spray pumps, and intravenous (IV) bags are among the most common packaging system components we evaluate. We welcome all routes of administration, including the more challenging prefilled syringes, blow-fill sealed vials, and laminated cans.
Thank you for your interest in learning more about extractable and leachable studies.
About the Author
Cheryl Johnson is the Commercial Development Manager of Biotechnology at Alcami. She has more than 15 years of industry experience in research and manufacturing scale laboratories. Her areas of expertise include analytical and preparative chromatography, method development and validation, and mass spectrometry with specialized knowledge of regulatory compliance relating to extractables and leachables. Cheryl joined Alcami in 2014 as a scientist and is a technical lead for Alcami's Biotechnology and Structural Chemistry related offerings.