New FDA Guidance on Biocompatibility

On September 20, 2024, FDA released draft guidance titled “Chemical Analysis for Biocompatibility Assessment of Medical devices”. The guidance includes recommended methodological approaches for chemical analysis for biocompatibility assessments with an objective of enhancing consistency and reliability of analytical chemistry studies. The recommendations are borne from FDA’s prior experiences in evaluating such studies which were included as part of premarket submissions.

Specifically, the guidance provides recommendations for the collection and reporting of chemical characterization data that could be used to support:

1. Screening for unspecified extractables (i.e., non-targeted analysis) or testing for specified extractables (i.e., targeted analysis) to evaluate certain biocompatibility endpoints (i.e., acute, subacute, subchronic, and chronic systemic toxicity, genotoxicity, carcinogenicity, and reproductive/developmental toxicity) in conjunction with TRA.

   
   

2. Chemical equivalency comparison to a device with previously demonstrated biocompatibility as part of a biological equivalency evaluation.

However, FDA fully recognizes that alternative approaches could be appropriate depending on device characteristics and intended use. When performing chemical characterization as part of a biocompatibility assessment for a device, manufacturers should consider FDA’s recommendations in this guidance, yet ultimately utilize an approach most conducive to their circumstances. Moreover, if there is device-specific FDA guidance or FDA-recognized consensus standards that address chemical characterization for a particular device (i.e. ISO 11979-5, ISO 18562-3, etc.), those recommendations and methods should be followed.

FDA’s recommendations contained in this guidance can be categorized broadly into the following subject areas:

• Information Gathering

  • Device Components and Materials

  • Test Articles, Control Articles, and Blanks

  • Test Article Processing Prior to Extraction

    
    

• Test Article Extraction

  • Extraction Conditions

  • Number of Extraction Replicates

  • Extraction Volume

  • Extraction Temperature and Time

  • Particulates

  • Additional Considerations for Exhaustive Extraction

    
    

• Chemical Analysis

  
  

• Suitability of Detection Methods

  • Reference Standards

  • Calibration, Sensitivity, and Quantification

  • Chemical Identification

    
    

• Data Reporting

  
  

FDA describes each of these subject areas in detail within the guidance document, and appendices are included to provide examples and further clarifications.

Should you require any assistance with biocompatibility assessments or with any quality or regulatory compliance matters with respect to your medical devices, please contact us at PRP. We’d be happy to work together!