2018 PDA Extractables and Leachables Training Course

Introduction on Extractables and Leachables

• What is the importance of a good E/L-qualification
• Historical cases of leachables, impacting the quality or the safety of a drug product
• Global regulatory requirements (FDA, EMA, etc.) for primary packaging

Understanding the Polymers Used in the Manufacture of Pharmaceutical Containers and Closures

• Types of polymers: examples in medical/pharmaceutical use
• Understanding the composition of polymers
• Making the distinction between compounds that are intentionally added to a material/polymer and not intentionally added substances

Understanding Glass as an Important Material Used in the Manufacture of Primary Packaging of Small Volume Parenterals

• Types of glass and their composition
• Additives added to glass, role and function
• Glass: the manufacturing process
• The issues with glass in parenteral applications
• Glass delamination and other quality issues with glass

The Mechanism of Leaching

• What are the physicochemical parameters to be considered when trying to understand polymer migration
• How do leachables move through a polymer, the diffusion model
• Special cases in migration

Helicopter View on the recent and Upcoming Changes to the US Pharmacopoeia (USP)

• USP <661> Plastic Packaging Systems and their Materials of Construction
• USP <661.1> Materials of Construction
• USP <661.2> Plastic Packaging Systems for Pharmaceutical Use
• USP <665> Polymeric Materials in Manufacturing of (Bio)Pharmaceutical Drug Products
• USP <1661> Evaluation of Plastic Packaging
• USP <1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems
• USP <1664> Assessment of Leachables Associated with Pharmaceutical Packaging/Delivery Systems

How to Perform a Safety Evaluation: Risk Assessment on Extractables and Leachables

• Toxicology 101
• EMA guideline on genotoxic impurities
• ICH M7 (DNA reactive Impurities) and it’s suggested staged approach.
• The Threshold concept of PQRI (OINDP and PDP/ODP)
• Examples

How to Set-up Extractable and Leachable Studies

• Designing extraction studies that are compliant with USP <1663>
• Selecting the right conditions for extraction
• How to select the right compounds to monitor in a leachable study?
• Designing a leachable study compliant with USP <1664>

Analytical Techniques to Perform Extractables and Leachables Research

• The importance of sample preparation: the corner stone in E/L research.
• What are the target compounds for material research?
• How does a classification of these compounds assist in finding the right analytical technique?
• From basic “screening” methodologies to state-of-the-art equipment:

E/L Testing for a Small Volume Parenterals (Liquid and LYO applications)

• Glass syringes: the issues with tungsten, glue residues and silicone oil and glass metals leaching
• The issue with rubbers: the plunger, the needle shield, or the tip cap: different approaches needed?
• The impact of secondary packaging: option or necessity?
• Setting up extractable and leachable studies for a pre-filled syringe
• Primary packaging for the lyophilized drug product – modus of interaction with the DP

E/L testing for Disposable and Single-Use Systems in Bioproduction

• How to classify the risk of different single use systems in the bioproduction process?
• Understanding BPSA and BPOG recommendations, and how they can be implemented in the study design
• Performing e/l studies on filters: potential approaches

Case Study Section

• Case study examples for primary packaging: pre-filed syringes, lyophilized drug product containers, blow-fill-seal applications, large volume parenterals, etc.
• Case study examples of the impact on secondary packaging: labels, printing inks, carton boxes, etc.
• Case study examples of single-use systems: bags, filters, tubing