USP Class VI: New Approach to Polymer Safety in Medical Devices

For decades, many medical device manufacturers have relied on USP Class VI certification when selecting polymeric materials for devices, components, or sterile packaging. If a supplier could provide a USP Class VI certificate, the material was often considered biologically safe and suitable for medical use.
However, the regulatory landscape has undergone significant evolution. With the latest updates in the ISO 10993-1 framework, this approach is no longer sufficient.

Today, regulators and notified bodies expect a science-based understanding of materials, their chemical composition, and their behavior during manufacturing and sterilization. In other words, biological safety can no longer rely solely on a certificate.

From “Material Certification” to Chemical Characterization

Historically, the USP Class VI standard evaluates materials using a series of in vivo biological reactivity tests performed on extracts of the material.
If no adverse biological reactions are observed, the material can be classified as Class VI.

While this approach has been widely used for decades, it has an important limitation as it does not fully describe the chemical composition of the material.
The modern regulatory approach instead focuses on chemical characterization, as described in ISO 10993-18.

Manufacturers are increasingly expected to identify and understand:

Additives and stabilizers.
Catalysts and polymerization residues.
Antioxidants and processing aids.
Contaminants and impurities.
Degradation products generated during manufacturing or sterilization.

Without this information, performing a proper toxicological risk assessment becomes difficult.
Essentially, a polymer may still be USP Class VI, yet be considered insufficiently characterized for regulatory submissions under current medical device frameworks.

The End of “Black Box Testing”

Another significant change in the ISO 10993 standard is the emphasis on the final configuration of the device rather than the raw material.
It was common to assume in the past that if the raw polymer was certified, the final component woulkd be safe, however, this assumption is no longer valid.

Medical device manufacturers must evaluate how manufacturing processes affect material chemistry, including:

Injection molding.
Extrusion processes.
Surface treatments or coatings.
Adhesives and bonding agents.
Sterilization processes.

Sterilization methods such as gamma irradiation, ethylene oxide (EtO), and vaporized hydrogen peroxide (VHP) can significantly alter the chemistry of polymers and potentially generate new extractables or degradation products.

This is why the ISO 10993 framework now emphasizes extractable and leachable studies, stability assessments, and aging simulations.
Understanding how a material behaves after processing and sterilization is essential for demonstrating safety.

Risk Assessment Instead of Animal Testing

The modern approach promoted by ISO 10993-1 encourages manufacturers to minimize animal testing whenever possible.

The evaluation follows a risk-based strategy combining:

Chemical characterization (ISO 10993-18).
Toxicological risk assessment (ISO 10993-17).
Existing scientific data.

The process works as follows:

Identify substances that may migrate from the material.
Estimate patient exposure.
Compare exposure with established toxicological thresholds.

If the calculated risk is acceptable, then further animal testing may not be necessary.
This approach not only has ethical benefits but also allows for a more scientifically informed approach to material safety.

The New Concept of “Reasonably Foreseeable Misuse”

The latest updates in the ISO 10993 framework also introduce a broader view of risk evaluation.
Manufacturers must consider not only the intended use of a device or packaging system, but also scenarios of reasonably foreseeable misuse.

Examples include:

Storage outside recommended temperature conditions.
Longer shelf life than expected.
Contact with unintended substances.
Variations during transport or sterilization cycles.

These factors can affect the chemical stability of materials and therefore must be considered during the biological evaluation process.

What This Means for Medical Device Manufacturers

For companies in the business of designing medical devices, components, or packaging, USP Class VI certification is not a viable approach anymore, at least as a standalone approach.

Companies should focus on ensuring their materials have been:

Chemical characterization data compliant with ISO 10993-18.
Toxicological risk assessments according to ISO 10993-17.
Extractables and leachables studies.
Stability and aging data after sterilization.
Full understanding of the material formulation.

These elements form the scientific basis of the Biological Evaluation Plan (BEP) and Biological Evaluation Report (BER) required during regulatory submissions.

Conclusion

The evolution of the ISO 10993 framework reflects a fundamental shift in how biocompatibility and material safety are assessed in medical devices.
The industry is moving away from simple material certification toward a deeper understanding of chemical composition, processing effects, and toxicological risk.For manufacturers, this means that material selection is no longer just a procurement decision, it is a regulatory strategy.

Working with experts in toxicology, chemical characterization, and regulatory affairs can significantly reduce risks during product development and streamline the path to regulatory approval. Contact us to learn more about how we can help you and be your partner.