Pace Analytical Life Sciences (PLS) has developed a comprehensive approach towards extractable and leachable testing. These studies identify extractables, compounds that can be extracted from a device under exaggerated conditions, and leachables, compounds that leach from a device in direct or indirect contact with the drug product or patient under normal use conditions.
Extractables and leachables may include both organic and inorganic compounds, typically coming from devices which may include additives such as lubricants, accelerators, monomers and high molecular weight oligomers from incomplete polymerization, residual solvents. Additionally, extractables can be formed from degradation products from temperature, absorption, hydrolysis, oxidation, corrosion or dissolution, or from the process itself like mould release agents and anti-static and anti-stick agents.
Extractable and leachable testing is particularly relevant to medical device packaging where safety and toxicology are being scrutinized. Leachables in devices may compromise patient safety.
EXTRACTABLES & LEACHABLES APPROACH
Our approach towards chemical characterization of extractables is to subject a device to worst-case conditions, and then characterize the constituents that are extracted from a component under these exaggerated conditions. Extraction conditions such as solvents, extraction time and temperature are chosen based on guidance such as ISO 10998-18. These extracts are then analyzed and semi-quantitated using the following techniques and instrumentation:
- Ultra Performance Liquid Chromatography-Photo Diode Array-Time of Flight Mass Spectrometry (UPLC-PDA-QTOF-MS) to identify non-volatile organic compounds.
- Direct Injection Gas Chromatography-Mass Spectrometry (DI-GC-MS) to identify semi-volatile organic compounds.
- Static Headspace Gas Chromatography-Mass Spectrometry (HS-GC-MS) to identify volatile organic compounds.
- Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) or Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) to identify elemental impurities.
- Non-Volatile Residue (NVR) analysis to establish exhaustive extraction conditions.
Once extractables are evaluated, a targeted leachables study can be developed to specifically quantitate compounds of concern that were identified in the extractables analysis. Methods to quantify leachables can be validated and used in long term stability studies. Additionally, simulation studies can be performed to determine potential leachables under accelerated conditions.
We are FDA registered, DEA registered, cGMP compliant, and ISO/IEC 17025 accredited.
Download Extractables/Leachables literature.
On Demand Webcast: Extractables and Leachables of Biopharmaceutical Container Closure Systems
As biopharmaceutical drug product development continues to grow, so do new regulations on packaging and container closure components associated with delivery of the drug product to the patient. This webcast will present a brief introduction to extractables and leachables (E&L), followed by a discussion of relevant United States Pharmacopeia and ISO guidelines and practical considerations when planning an extractables and leachables project.
Topics covered in this webinar:
- Review results and analysis of an E&L case study of biopharmaceutical single-use bag systems
- Gain an overview of the process, procedures, and approaches for biopharma E&L studies
- Understand analytical capabilities and expertise needed to conduct effective studies
Daniel Abate, Ph.D.
Hannah Tims, PhD.