Jun 21, 2016

Final guidance issued by the US Food and Drug Administration clarifies and expands on how manufacturers of medical devices that come into contact with the human body should comply with the ISO 10993-1 standard for biological evaluation of devices within risk management frameworks.

FDA guidance on ISO 10993-1 compliance has not been updated since 1995; the final guidance includes several new recommendations for manufacturers in terms of risk-based biocompatibility approaches, chemical assessment and biocompatibility test article preparations for devices utilizing nanotechnology.

Risk-based approaches to biocompatibility

The agency’s recommendations for risk-based biocompatibility evaluation are based on elements of ISO 10993-1:2009. Specific steps that such an approach involves for manufacturers include:

  • Risk assessment: A finished device should undergo risk assessment; device materials, processing of materials and manufacturing methods should all be included in this assessment.
  • Risk identification: Manufacturers should account for potential risks including not only chemical toxicity but also physical device characteristics as well as processing parameters that may pose risks to patients and users.
  • Available risk information: Manufacturers should check to see whether existing information such as literature, standards, clinical and pre-clinical data can adequately identify and mitigate risks posed by their own devices in order to avoid unnecessary additional testing.
  • Submission: Manufacturers should submit their risk assessments at the beginning of the biocompatibility sections of their applications to the Center for Devices and Radiological Health (CDRH). Clear connections between applicants’ identified biocompatibility risks and data available to mitigate those risks should be made in these submissions.  All biocompatibility testing and evaluation methods used to mitigate risks should be well documented.

FDA versus ISO 10993-1 compliance

As is the case with many other US medical device regulations, FDA biocompatibility testing guidance may be based on and highly similar to the ISO 10993-1 standard, but not identical.

(For in-depth information of the ISO 10993 standard for biocompatibility, download our whitepaper on the topic.)

“In general, FDA agrees with the framework established in ISO 10993-1 for identification of the nature and duration of contact… However, FDA has made several modifications to the evaluations identified in that standard,” states the FDA, pointing readers to Section IV.D and Attachment A of its new guidance for additional details of these modifications.

“-Free” labeling concerns

One issue raised in the new guidance that manufacturers should note pertains to device labels claiming that a product is “latex-free,” “BPA-free” or some other kind of substance “-free.” The FDA casts doubt on existing testing methods’ ability to prove that a device is completely free of any particular allergen or toxic substance, and instead recommends that firms use the phrase “Not made with [substance.”

However, manufacturers should only use such verbiage on their labeling if it can apply to the entire device as well as all of its packaging—otherwise, manufacturers should specify which components of their products are not made with a particular substance.


  • Stewart Eisenhart