Extractable & Leachable Studies

Regulators are concerned with substances migrating from different materials (polymers, metals, glass etc.) which patients may be exposed to through many different routes of administration, such as:
  • Orally Inhaled Nasal Drug Products
  • Parenteral
  • Production equipment – Single Use Systems
  • Medical Devices

Analytical Techniques Studies

Analytical Techniques for Extractables and Leachables Studies
Numerous analytical techniques are used for E&L studies because no single analytical technique can detect them all.
  • Gas Chromatography Mass Spectrometry (GC-MS)
  • 3D Gas Chromatography Mass Spectrometry (GCxGC-ToF-MS)
  • Liquid Chromatography Mass Spectrometry (LC-MS)
  • pH
  • Conductivity
  • Non-Volatile Residue (NVR) and Fourier Transform Infrared (FT-IR) spectroscopy
  • Total Organic Carbon (TOC)
  • Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES)
  • Ion Chromatography (IC)

In order to obtain successful regulatory approval for new drug applications, packaging interactions with the drug product should be evaluated to ensure product safety.

The degree of interaction between the drug product and the primary packaging is dependent on the product type, as is the risk to the patient. Chromak Research follow best practice guidelines, such as those provided by the PQRI for OINDP and USP chapters 1663 and 1664.

The Extractables study

  • Design and execution of the extractables study on critical components of the primary packaging, covering inorganic and organic extractables.
  • Determination of the Analytical Evaluation Threshold (AET) from the Safety Concern Threshold (SCT)
  • Use of a number of extraction methods, employing multiple analytical techniques, as no one analytical technique is capable of detecting all extractable substances
  • Provision of a detailed technical report, containing full results and chromatograms
  • Option for undertaking a literature based toxicological assessment of the detected extractables to identify target leachables

The Leachable study

  • Development and validation of methods for the assessment of leachables in the drug product according to ICH Q2(R1)
  • Analysis of stability time point samples for leachables