The Food and Drug Administration (FDA) has published a guidance document providing standards specific information on biocompatibility testing of the medical device in the context of the Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program. 

Regulatory Background 

The present FDA guidance is intended to provide medical device manufacturers and other parties involved with the additional information regarding the biological evaluation of medical devices and the way the appropriate standards should be applied under the ASCA Pilot Program framework. In particular, the guidance contains a list of the FDA-recognized voluntary consensus standards allowed to be used for biocompatibility testing of medical devices in the context of the ASCA Pilot, the program specifications for the aforementioned standards, and also certain recommendations regarding the information to be included in the premarket submission in the part of biocompatibility testing in case if such testing has been performed by an ASCA-accredited testing laboratory. Some additional aspects related to biocompatibility matters are also described in the appropriate FDA guidance on the application of International Standard ISO 10933-1. At the same time,  some types of medical devices requiring customized sample preparation are actually falling outside the scope of the ASCA Pilot. The list of excluded devices also includes liquid devices, creams, gels, hydrogel devices, and ones containing nanomaterials. 

According to FDA guidance, biological evaluation is a process of assessing the biocompatibility-related risks of medical devices with direct and/or indirect contact with human tissue. In case if such an assessment is required due to the type of medical device in question, the manufacturer may refer to the appropriate voluntary consensus standard to demonstrate conformity with the applicable requirements. In the present guidance, the Agency provides an exhaustive list of the FDA-recognized consensus standards related to biocompatibility testing of medical devices, allowed to be used under the ASCA Pilot Program framework. Besides the particular standards, the document also outlines eligible test methods. The Agency also mentions that each standard has its own extent of recognition (partial or complete). Such information could be found in the Supplemental Information Sheet (SIS) accessible via the FDA Recognized Consensus Standards Database. The Supplemental Information Sheet also contains additional information to be considered by the medical device manufacturer when applying the particular standard in the context of premarket submission.

Biocompatibility Testing and ASCA Accreditation

According to the rules set forth under the ASCA Pilot Project, in order to be edible of biocompatibility testing under the aforementioned framework, the testing laboratory should be duly accredited by the ASCA-recognized accreditation body. In order to assist testing laboratories in achieving and sustaining compliance with the applicable requirements, the FDA provides a detailed list of eligibility criteria a laboratory should meet. In particular, the accreditation would be performed in accordance with the standards ISO/IEC 17011 and ISO/IEC 17025:2017: General requirements for the competence of testing and calibration laboratories, and also the specifications provided by the Agency in the present guidance on biocompatibility testing. 

The standard ISO/IEC 17025 describes the general requirements the laboratory shall meet, including ones related to the personnel, premises, and equipment. More specific requirements are set forth by the standard ISO 10993-1 Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process. The aforementioned standard describes in detail the procedures to be performed by the laboratory in the course of sample preparation. The Agency also provides the pre-defined criteria for positive/negative/reference control values to be taken into account by the laboratory. 

One of the most important aspects described in the present FDA guidance on biocompatibility testing relates to the reporting of results. According to the document, the following information should be recorded:

  • Test procedure(s) and test standard(s) used,
  • Product or component(s) tested,
  • Test equipment used for testing, measurement, or review (including the equipment`s rating and accuracies, unless otherwise readily available),
  • Date of the test(s). For example, periodic controls may have different test dates,
  • Test report number, including revision number and amendment date, if applicable, and any related sub-contracted test report number(s),
  • Names of the personnel performing the test(s) and the names of all supervisory personnel involved in the study and for biological studies, the signature of the study director and quality assurance unit personnel,
  • The test conditions as specified by the test standard, if applicable,
  • Sample preparation,
  • Extraction conditions, if applicable,
  • Sample manipulation,
  • Test results, including opinions and interpretations, all applicable data, and a statement that the testing was conducted according to 21 CFR 58 Good Laboratory Practices for Nonclinical Laboratory Studies regulations. 

Upon completion of biocompatibility testing, the laboratory shall provide the complete test report to the medical device manufacturer, together with the ASCA Summary Test Report.

Content of the Premarket Submission 

The FDA also provides certain recommendations regarding the content of the premarket submissions related to biocompatibility testing under the ASCA Pilot. According to the document, the submission shall contain the following elements: 

  1. Cover Letter,
  2. Declaration of Conformity, 
  3. Supplemental Documentation. 

As it was already mentioned before, the ASCA-accredited testing laboratory provides a test report to the medical device manufacturer, while the latter includes the information and conclusions contained therein to the declaration of conformity. At the same time, the FDA is entitled to require the manufacturer to provide additional information or the complete test report in case if it would be necessary to assess biocompatibility-related matters associated with the medical device subject to review. In certain cases, the Agency may also require the testing laboratory and/or the manufacturer to provide a rationale to support a decision on a premarket submission. In order to meet the admissibility criteria, the testing report should be based on the biocompatibility testing conducted by the ASCA-accredited laboratory in accordance with the consensus standards and specifications described here above. In case of any deviations, the FDA recommends providing a complete test report ab initio. The document also contains a list of particular situations in which the provision of a complete test report is strongly recommended to accelerate and simplify the regulatory procedures. For instance, this would be required in case of adverse events occurred during the biocompatibility testing. 

Besides the points described here above, the FDA guidance on biocompatibility testing for medical devices also contains an example of the ASCA Declaration of Conformity for Biological Evaluation of Medical Devices Standards in the ASCA Pilot. The example is provided to describe the elements to be included in the declaration of conformity to be submitted by the medical device manufacturer as a part of the premarket submission. 

Summarizing the information provided herein, the guidance dedicated to biocompatibility testing and evaluation for medical devices covers the most important aspects to be considered by both medical device manufacturers and testing laboratories intended to be accredited to conduct biocompatibility testing under the ASCA Pilot Program framework. In particular, the document describes the eligibility criteria the laboratory shall meet when applying for ASCA-accreditation, and also provides recommendations regarding the content of premarket submission to be filed by the medical device manufacturer.

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