PDA Extractables and Leachables Training Course

Thursday, 27 March 2025

09:00
Introduction and Attendee Expectations

09:15
Introduction on Extractables & Leachables (E/L)

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

10:30
Coffee Break

10:45
Understanding the Materials, Used in the Manufacture of Pharmaceutical Containers & Closures

• Types of polymers – examples in medical/pharmaceutical use
• Understanding the composition of polymers: Intentionally added & Non-Intentionally added Compounds: Their function and origin
• The issues with glass in parenteral applications

11:30
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

12:00
Lunch Break

13:00
How to Set-up Extractables & Leachables Studies Pharmaceutical Container Closure Systems

• Selecting the right conditions for extraction
• How to select the right compounds to monitor in a leachable study
• Designing a leachable study

14:45
Coffee Break

15:00
Analytical Techniques to Perform Extractables & 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

15:45
How to Perform a Safety Evaluation – Risk Assessment on Extractables & Leachables

• Toxicology 101
• EMA Guideline on Genotoxic Impurities
• ICH M7 (DNA reactive Impurities) and its suggested staged approach
• The Threshold Concept of PQRI (OINDP and PDP/ODP)
• Examples

17:00
End of Training Course Day 1

Friday, 28 March 2025

08:30
Recap Day 1

08:45
E/L Testing for a Small Volume Parenteral Container Closure systems

• 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 & leachable studies for a pre-filled Syringe
• Biological Drug Products versus Small Molecule Drug Products
• Primary packaging for the lyophilized drug product – modus of interaction with the DP
• Critical aspects when designing leachable studies for lyophilized DP
• Reactivity Of Leachables: concern for Lyophized drug Products
• Integration of the administration procedure (e.g. IV-set, pump system) in leachables evaluation

10:00
Coffee Break

10:15
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 & BPOG recommendations, and how they can be implemented in the study design
• Performing E/L studies on filters: potential approaches

11:00
Large Volume Parenterals

• The challenge in E/L testing for LVP’s
• Primary packaging for LVP’s – critical materials and components
• Secondary packaging for LVP: critical points to consider

11:30
Lunch Break

12:30
Qualification of Injection Devices used for Parenteral Administrations

• Short introduction into Medical Device Regulations (ISO 10993 series)
• Difference in Approaches for Medical Devices, compared to Pharmaceutical Packaging
• Considerations for Combination Products: how to proceed?

14:00
Coffee Break

14:15
Updates of E/L- Regulations, Standards and Recommendations

• Pharma Packaging:
  o Final PQRI recommendations of the Parenteral Drug Product (DPD) Chemistry group
  o USP <661> & USP<665> chapters: where are we, where could it go to?
• (Bio)Pharmaceutical Manufacturing
  o The BPOG protocol

15:45
Q&A

16:00
End of Training Course