Best Practices for Conducting Extractable and Leachable Studies

Regulatory agencies expect that any container closure systems or components utilized in manufacturing the drug product do not adulterate the product. Extractable studies are performed to evaluate the potential for various chemicals to migrate from container closure or manufacturing systems into pharmaceutical products. Appropriately designed extractables studies provide relevant and meaningful data, allowing for a detailed risk assessment.

Several different extraction solutions and analytical techniques may be employed to screen the components of interest for extractable compounds. Some solvent/product matrices may interfere with the testing and present challenges for the analytical techniques performed. Care must be taken in evaluating these matrices to ensure that potential extractable compounds are capable of being observed.

Data generated from an extractable study should be evaluated to determine the toxicological concern of the extracted compounds. Compounds are assessed using a step-wise approach from a definition of threshold to the evaluation of tolerable exposure.

During this presentation, you will learn:

• Strategies for establishing an extractables study design
• Risk assessment based on product type
• Use of various analytical techniques and their benefits and drawbacks
• Tools utilized to handle difficult sample matrices
• Tools to handle Threshold of Toxicological Concern (TTC)
• Data sources useful for toxicological evaluation
• Tools to evaluate Tolerable Intake (TI) and Tolerable Exposure (TE)
• Design of studies to monitor leachable compounds

Speakers

Thomas C. Lehman, Ph.D., Manager, Method Development and Validation, Eurofins Lancaster Laboratories, Inc.

Dr. Lehman has more than 20 years of analytical testing experience, including 10 years performing extractables and leachables projects. As manager of the Method Development and Validation Group, he oversees the analytical development and validation of preclinical to marketed products, including extractables and leachables testing and peak identification projects utilizing mass spectrometry. Dr. Lehman served as a member on the Bio-Process Systems Alliance Extractables and Leachables Subcommittee, which authored guidance documents on evaluating extractables and leachables for single-use, disposable bioprocessing materials. He earned a B.S. in biochemistry from Elizabethtown College and a Ph.D. in chemistry from the University of Delaware.

Message Presenter

Erica J. Tullo, Ph.D., Senior Chemist, Method Development & Validation, Eurofins Lancaster Laboratories, Inc.

Dr. Tullo has five years of experience performing extractables and leachables testing for Eurofins Lancaster Laboratories. She helps in designing experiments to meet each client’s unique needs. She specializes in LC/MS and GC/MS testing of various types of materials, including final container closure systems and bioprocessing components. Ms. Tullo earned a B.S. in chemistry from Washington College, a M.S. in chemistry and a Ph.D. in applied science from the College of William and Mary in Virginia.

Message Presenter

Paolo Pescio, Medical Devices & Toxicology Manager, Eurofins Biolab, Inc.

Paolo Pescio has nearly 10 years of experience performing pre-clinical evaluation for medical devices. He serves as Chairman of the UNI U4201 Committee for non-active medical devices for transfusion and biological evaluation and is also active as member of ISO TC194 and CEN TC206 groups. He is in charge of tox activities in Euorfins Biolab, and his expertise lies in In Vivo study design, toxicological evaluation experimental toxicology and risk assessment. He earned a M.S. in Biomedical Engineering from Polytechnic University of Milan.

Message Presenter