Strategic Information Gathering for Medical Devices: The Forensic Investigation Team of “ISO 10993”

In today’s medical device landscape, biocompatibility is no longer a checkbox-it’s a strategic pillar of product safety and regulatory success. With the upcoming release of the latest revision to ISO 10993-1 (currently a Final Draft International Standard (FDIS)), the integration of chemical characterization (ISO 10993-18) and toxicological risk assessment (ISO 10993-17) is more critical than ever. These standards now align closely with ISO 14971:2019 Medical devices-Applications of risk management to medical devices, embedding biological evaluation into the broader risk management framework.

The Shift in Perspective: ISO 10993-1:2025 introduces new terminology:

·       Biological hazards

·       Biologically hazardous situations

·       Biological harms

These must be identified and assessed using chemical and toxicological data, reinforcing the need for a risk-based, science-driven safety narrative.

Imagine you're leading a high-stakes forensic investigation to determine whether a new material is safe to introduce into the human body. You’ve got three expert agents on your team including yourself as the lead investigator:

Agent 10993-1: The Lead Investigator scopes the case—defines contact type, duration, and anatomical site, then decides which risks need to be investigated.

ISO 10993-1 sets the stage by defining a systematic framework for evaluating biological risks. It emphasizes:

•                     Risk-based evaluation: Not all devices require comprehensive testing. Instead, manufacturers must assess the clinical context including target patient population, the nature, duration, and type of body contact to determine relevant endpoints.

•                     Use of existing data: Gather information on the materials, design, intended use, and function. Don’t forget the manufacturing process including additives, residuals, sterilization methods, and packaging. Evaluate the chemical and physical properties including surface area, porosity, degradation potential. Historical data, including literature, and prior testing can reduce the need for new animal studies.

•                     Integration with chemical characterization: ISO 10993-1 explicitly calls for chemical data (note: chemical data can include existing data) to inform toxicological risk assessments.

Strategic takeaway: Start with the end in mind. A well-structured biological evaluation plan (BEP) aligned with ISO 10993-1 can streamline testing, reduce costs, and improve regulatory outcomes.

Agent 10993-18: The Chemist is in the lab, identifying extractables and leachables, flagging anything suspicious for toxicological review.

ISO 10993-18 dives deep into extractables and leachables, guiding how to identify and quantify chemical constituents that may migrate from a device under clinical use conditions. Key principles include:

•                     Analytical threshold setting: Establishing reporting thresholds based on toxicological relevance (e.g., TTC).

•                     Non-targeted analysis: Balancing broad screening with focus to identification of known and unknown risks.

•                     Use of orthogonal methods: Employing complementary techniques (HS-GC-MS, GC-MS, LC-MS, ICP-MS) to ensure comprehensive coverage.

Strategic takeaway: Chemical characterization is not just a lab exercise—it’s a risk narrative. The goal is to generate data, both expected and unexpected, that feeds directly into toxicological risk assessments under ISO 10993-17.

Agent 10993-17: The Toxicologist interprets the evidence, calculates safe exposure limits, and delivers the final risk verdict.

ISO 10993-17 provides the framework for toxicological risk assessment, using data from ISO 10993-18 to:

•            Establish safe exposure limits (e.g., PDEs or TTC-based thresholds)

•            Assess cumulative risk from multiple chemical constituents

•            Justify whether additional biological testing is needed

Strategic takeaway: Toxicological risk assessment is the linchpin of biocompatibility justification.

Together, they solve the safety puzzle.

 10993-1 asks the right questions

 10993-18 gathers the chemical clues

 10993-17 delivers toxicological outcome

Without all three, the case is incomplete. But when they work together, they build a defensible, science-driven safety narrative that regulators trust.

Why it matters: This shift makes chemical characterization and risk assessment central to the device’s safety narrative—not just supporting documentation.  These 3 key  standards in the ISO 10993 series guide how we assess and document biological safety: ISO 10993-1 (Evaluation and Testing) and ISO 10993-18 (Chemical Characterization) and ISO 10993-17 (Risk Assessment). Together, they form a risk-based team that’s both scientifically rigorous and regulator-ready.

Tips for Strategic Info Gathering

•                     Leverage prior knowledge: Use historical data, predicate devices, and literature to justify test plans.

•                     Engage early with toxicologists: Their input can shape extractables thresholds and risk assessments.

•                     Think like a reviewer: Anticipate questions and build a narrative that connects chemistry, biology, and clinical relevance.

Strategic information gathering under ISO 10993-1, -18, and -17 isn’t just about compliance, it’s about credibility. By aligning chemical data with biological risk, manufacturers can build a robust safety case that satisfies regulators and protects patients.

Whether you're launching a new device or refining an existing submission, a thoughtful, integrated approach to biocompatibility can be your competitive edge.