Enhancing Product Safety in Medical Innovation. Contact Gateway Analytical to ensure product integrity and compliance!
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.
Extractables and leachables (E&L) refer to the study of potential chemical compounds that can migrate from a product, such as a drug or medical device, into the environment or patient. E&L studies are integral to ensuring the safety and efficacy of pharmaceutical products to prevent adverse reactions or toxicity that could arise from such contaminants.
Extractables are chemical compounds isolated from products under controlled laboratory settings, while leachables are those that can naturally migrate from the product into the surrounding environment or directly into the patient during usage.
Explore how Gateway Analytical provides E&L services for pharmaceuticals and medical devices, including method development and validation, impurity identification, materials characterization, and regulatory support.
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
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
- Nitrosamines analysis
COMPONENT SELECTION PACKAGE
- Extractables Data Packages
- Component Qualification Strategies
- Technical Assessment Reports
PHARMACEUTICAL DEVELOPMENT
- Customized Extraction Studies
- Migration Studies
- Formulation/Stability Support
- Risk Assessment Reports
- Customized Extraction Studies
- Migration Studies
- Formulation/Stability Support
- Risk Assessment Reports
REGULATORY SUPPORT
- Leachable Study Performed on Stability (nominal & accelerated conditions)
- Component Change Control Studies
- Regulatory Support
INSTRUMENTATION
- LC-MS
- GC-MS
- GC-HS
- HPLC-UV
- HPLC-PDA
- UPLC
- FTIR
Component Reference
- Coated Stoppers
- 13 & 20 mm Stoppers
- Serum Stoppers
- Lyophilized Stoppers
- Ready to Use (RTU)
- Ready to Sterilize (RTS)
- UDS Stoppers
- Plungers
Frequently Asked Questions
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.