Introduction to Extractables & Leachables Testing

Overview

This course will give participants an understanding of how polymeric materials are used in pharmaceutical products and how additives and other materials related to those polymers i.e. the extractables and leachables, may be of concern or risk to the patient.

The course will also cover the regulatory aspects and requirements relating to E & L, and will highlight some of the guidelines developed to assist medical companies in defining strategy and limits for testing.

Analytical methodology, instrumentation and sample preparation will be discussed and the basic steps required for performing an E & L study will be described, including stability plans and method validation. Case studies will be used to demonstrate the processes involved.

Course Content

Background to Polymers

• Discussion of polymeric and elastomeric materials available for use, and where and why the various polymers are used.
• Polymer additives, potential impurities and the reasons for their presence.
• Review of polymer processing
• Regulations and Guidelines
  • Why we are interested in extractable and leachables
  • Why we have to test for extractable and leachables
  • Regulatory standpoints and requirements
  • Working groups and guidance documents
• Introduction to Extractable and Leachables
  • Definition of extractables and leachables
  • How extractable compounds become leachables
  • Factors affecting the migration of compounds
• Analytical Techniques & Approaches:
• Component review & selection of critical parts
• Aim of extractable study
• Extraction methods, including solvent choice and sample preparation techniques.
• Analytical techniques overview:
  • gas chromatography mass spectrometry (GC-MS)
  • liquid chromatography mass spectrometry (LC-MS/UV)
  • non volatile residue (NVR)
  • Fourier transform infra spectroscopy (FT-IR)
  • Inductively coupled plasma atomic emission spectroscopy (ICP-AES).
  • Extractable study case studies
  • Laboratory tour

• Leachable Method Development & Validation

• Leachable method development:
  • Selection of extractable / leachable compounds
  • Development of leachable analytical methods
• Leachable method validation:
  • Aim
  • Guidance / standard review
  • Validation parameters discussion
  • How to execute validation
  • Validation case studies
• Leachable studies:
  • Stability storage overview
  • Leachable time point analysis