Extractables & Leachables
Offering customized elastomeric component assessment services to ensure the functionality, safety, and compatibility of drug products, manufacturing materials, and container closure systems through various stages, from Phase I to post-market approval
Understanding where our services are desired and made most effective is our #1 priority. Download our Materials Analysis Process Poster today to learn more.
Gateway Analytical’s team engages with customers to help design and support the extractables/leachable studies that are best suited your drug product. We can assess functionality for intended use, extractables and leachables, and physical chemical compatibility. Gateway Analytical provides dedicated support for migration, extractable, and leachable, study design utilizing a combination of placebo, active drug product, and/or aggressive solvents to help you identify potential leachables and to optimize your formulation. We keep your product moving forward through stability studies, regulatory approval, and post-market assessment
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Current Analysis Capabilities
Fully compliant with cGMP / 21 CFR Part 11 / ISO 17025
Non-volatile compound analysis via high-resolution accurate mass spectrometric instrumentation (Waters G3 QToF, coupled to a Waters Acquity UPLC with PDA)
Allows for compound identification as well as the generation of molecular formulas using accurate mass and isotope spacing information, for any previously unknown ionizable compound
MS/MS fragmentation capabilities to further drive structural elucidation
We can perform positive analyte confirmation with the use of analytical standards, combined with chromatographic retention time, accurate mass/isotope spacing, and fragmentation pattern information
Semi-volatile compound analysis via direct injection ALS GC-MS
Volatile compound analysis via headspace sampling GC-MS
Elemental impurity analysis via ICP-MS through fully audited and qualified partner laboratories
Compound identification and deconvolution capabilities supported by the NIST/Wiley 2020 Mass Spectral Library
We can support assay testing, targeted trace analyses, and known and unknown impurity characterization/identification
Intact mass analysis of proteins, peptides, MS/MS sequencing, as well as examination of various post-translational modifications
Contact us today and tell us how we can help analyze the materials you rely on each and every day for your business.
Product Life Cycle Support
COMPONENT SELECTION PACKAGE
Extractables Data Packages
Component Qualification Strategies
Technical Assessment Reports
Customized Extraction Studies
Risk Assessment Reports
- Leachable study performed on stability (nominal & accelerated conditions)
- Component Change Control Studies
- Regulatory Support
Extractables & Leachables FAQs
We use the term “Extractable” to refer to any compound can be extracted from the packaging/manufacturing materials of interest under both the nominal conditions of use, as well as under additionally aggressive extraction conditions, which can help facilitate compound identification, and provide a worst-case extractable scenario.
A “Leachable”, refers to a compound that is observed to leach into the drug product from the packaging and/or container closure system under expected storage conditions.
Leachables, or the leachable profile of a drug product refers to the list of compounds that are observed to leach into the drug product from the packaging and/or container closure systems that contain the drug product.
In an extractable study, we can perform extractions on materials involved in the packaging and manufacturing of the drug product that have the potential to impart leachables into the system (including primary and secondary container closure systems).
Each material can be treated with a variety of extraction solvents that allow us to investigate the anticipated contacting media for that material, as well as additionally aggressive solvents to provide a “worst-case” evaluation.
All of the extractable compounds observed in excess of the predetermined limit (Analytical Evaluation Threshold, or AET) are then reported, along with any available structural information to support identification and risk analysis.
In a leachable study, a set of drug product samples are aged at nominal and/or accelerated stability conditions in the final container closure system and are evaluated for leachables at multiple timepoints. The purpose of this study is to screen the
samples for any leachables over time at the accelerated and actual conditions of storage.
Any leachables observed during this study in excess of the pre-determined limit (Analytical Evaluation Threshold, or AET) are then reported, along with any available structural information to support identification and risk analysis.
We recommend performing extractable studies once the manufacturing and assembly process for your drug product is determined to ensure the data is as relevant and useful as possible to support your regulatory submissions.
Leachable studies should be initiated as soon as possible following selection of your final container closure system. This is recommended to avoid any potential delays as these studies require aging of the drug product on stability, which can take up to two years at nominal conditions.
The most commonly observed extractable and leachable compounds in pharma are those associated with extended exposure to the drug product, and would include a variety of antioxidants, plasticizers, slip agents, lubricants, etc. Examples of components that can significantly contribute to the extractable and leachable profile of your drug product are any vial stoppers, spray pumps, and other plastic primary packaging components. Inks components have been known to migrate through the secondary packaging and into the drug product but is far less common. Evaluation of both the primary and secondary packaging componentry is key to ensuring drug product safety.