This course provides an in-depth exploration of the chemical characterization process essential for assessing the biocompatibility of medical devices. Participants will gain insight into the latest regulatory expectations worldwide, with a focus on compliance with ISO 10993-17, ISO 10993-18, and industry best practices. The course will cover key areas, including the fundamentals of polymers and materials science, the extraction and data collection process for extractables and leachable’ s (E&L), and the toxicological risk assessment of E&L data. Through a structured curriculum, participants will learn to navigate the complexities of chemical characterization step-by-step, ensuring they can effectively address regulatory requirements and enhance the safety profiles of medical devices.

I. Introduction to ISO 10993-1, ISO 10993-17, and ISO 10993-18

• Chemical characterization in lieu of animal testing for systemic toxicity, reproductive toxicity, genotoxicity, carcinogenicity

II. Extent of recognition of chemical characterization (ISO 10993-18 and -17) in the US, EU, and other regions

III. Examples of chemical characterization deficiency comments by regulatory agencies

IV. Fundamentals of polymers/materials science

• Basics of organic chemistry 
• Monomer vs Polymers and their relation to medical devices 
• Polymers: Thermosets vs Thermoplastics
• Common Polymeric Systems: Synthesis/Preparation Methods/Formulations 
  • Thermoplastics (i.e. PP, HDPE, Acetal, PEEK)
  • Thermosets (i.e. silicone-based materials, adhesives)
• Coatings for Medical Devices (i.e. hydrophilic/hydrophobic)
• Processing Aids (i.e. mold-release agents; solvents)
• Other Materials: Metals, Drugs, Biologics, Biobased, and Gases
• Effect of Time and Exposure Environment on a Material's Safety Profile
  • Potential Degradants and Side Products of Common Materials

V. ISO 10993-18: Extractables and Leachable's (E&) & Analytical Chemistry 

• Basics of Extractions: Solvent Selection, Temperature, Time, pH, Ratios, Materials Effect
• Exhaustive vs Simulated Extractions
• Challenges with Exhaustive Extraction
• Solvent Selection for Extractions
• Introduction to analytical chemistry (HS-GC/MS; GC/MS; LC/MS; ICP/MS)
• Application and Calculation of AET
• Identification and Quantification of Extracted Chemicals
• Addressing Unknown Chemicals
  • Benefit of Priori materials/device assessment
• Tips for Screening a Laboratory: Protocol and Report

VI. Toxicological Risk Assessment in Relation to ISO 10993-17

• Data Sorting and Cleaning for Risk Assessment (e.g., Grouping Chemicals)
• Using TSL vs TI to Establish Chemical Safety
• How to find relevant toxicological safety information for an identified constituent/chemical? 
• Deriving TI and MOS for Chemicals
• How to leverage MOS and other literature to determine safety of a chemical for a biocompatibility endpoint? 
• Handling Chemicals with No Data
• Fundamentals of Surrogate Selection for No-Data/Low-Data Chemicals
• Tips for a Complete Toxicological Risk Assessment

VII. Case Studies and Practical Exercises

Over the course of sixteen (16) hours, the attendee/learner will be able to:

1. Understand Fundamentals for Polymers/Materials Relatable to Medical Devices:
   • Gain a solid understanding of polymer science fundamentals, including the differences between thermoplastics and thermosets and common formulation additives, coatings, processing aid, and potential degradants. 
   • Learn how these factors impact the safety and biocompatibility of medical devices.
     
     
2. Understand Extractables and Leachable’ s (E&L) Profiling of Medical Devices:
   • Learn the essential practices and methodologies for E&L profiling, including solvent selection, the effects of materials of construction, and the impact of extraction conditions (time, temperature, pH). 
   • Understand how E&L studies are carried out and assess laboratory capabilities to ensure compliance with ISO 10993-18.
     
     
3. Understand Process of the Toxicological Risk Assessments of E&L Data:

   • Acquire the skills to use E&L data in conducting toxicological risk assessments (TRA) as per ISO 10993-17. This includes grouping chemicals, deriving tolerable intake, and handling chemicals with limited data.

   • Evaluate whether TRAs meet regulatory standards and ensure the safety of medical devices.

Professionals in the medical device industry with expectations to comment or carry out biocompatibility-related tasks in their position such as:

• Regulatory Affairs and Quality Assurance Professionals
• Research, Design and Manufacturing Engineers
• Microbiologists and Chemists involved in the evaluation of Medical Devices
• Product Managers, Laboratory Managers
• Process Development and System Engineers
• Toxicologists and Biological Safety Specialists