The Food and Drug Administration (FDA) has published draft guidance on updates for biocompatibility of certain devices in contact with intact skin.


The public consultations period commenced on October 15, 2020, and would last for 60 days during which the industry representatives may submit their comments and suggestions. Upon finalizing the recommendations, the Agency will make the appropriate amendments to the guidance on the application of the International Standard ISO 10993-1 related to the biological evaluation of medical devices

The authority also mentions that due to the legal nature of the guidance, its final version would not establish any enforceable requirements the manufacturers shall follow since it only provides certain recommendations to be considered. Hence, another approach could be also used, providing that such an approach is agreed with the authority and complies with the applicable requirements.

Regulatory Background 

The present draft guidance is intended to introduce certain amendments to the recommendations on the biocompatibility information to be provided by the medical device manufacturers in the course of filing a premarket submission. In particular, by issuing the guidance, the FDA addresses the issues related to the medical devices containing polymers and fabrics that are in contact with intact skin. At the same time, the aforementioned guidance on the biological evaluation of medical devices remains valid until the present guidance would be finalized by the authority. Moreover, the sections of the initial guidance on biocompatibility-related matters, that are not covered by the present draft guidance will remain in force. The document also contains references to the FDA-recognized voluntary consensus standards the manufacturers may use to demonstrate compliance of the medical device in question with the applicable requirements set forth therein. 

The issues covered by the present FDA draft guidance on certain biocompatibility aspects are related to:

  • the premarket approval applications (PMAs), 
  • humanitarian device exemption (HDE) applications, 
  • investigational device exemption (IDE) applications, 
  • 510(k) premarket notification submissions, and 
  • De Novo classification requests. 

All the points above are related to the applications containing patient-contacting elements since in such cases an additional assessment is required to evaluate the potential impact of the materials used and the biological response of the patient’s organism.

New Attachment to the Biocompatibility Guidance 

According to the information the FDA already has, the skin-contacting materials made from polymers and fabrics have a long history of safe use, so the biocompatibility risk associated thereto is deemed to be relatively low. In such cases, the Agency is mostly focused on obtaining sufficient rationales to justify the omission of biocompatibility testing. The attachment outlines the least burdensome approach to be applied by medical device manufacturers to achieve and sustain compliance in the context of biocompatibility testing. The authority also emphasizes the importance of the «3Rs» approach: to reduce, refine, and replace animal use in testing when feasible. The approach described by the FDA is also based on the principles introduced by the Quality System Regulation (QS Regulation, 21 CFR 820). 

As prescribed by the applicable regulations, all biocompatibility issues associated with the devices containing patient-contacting elements should be duly recorded and indicated in the Device Master Record. The responsibilities of the medical device manufacturer are covering, inter alia, the following aspects: 

  • Purchasing controls over material suppliers (21 CFR 820.50).
  • Production and process controls for manufacturing (21 CFR 820.70). In accordance with these requirements, all the materials that could lead to additional biocompatibility risks should be removed or limited to the lowest extent in order to mitigate such risks.
  • Receiving, in-process, and finished device acceptance (21 CFR 820.80) for components and manufacturing materials. 
  • Analysis of quality data (21 CFR 820.100(a)(1)). According to the document, such an analysis should cover the analysis of complaints to be performed in order to identify quality problems (e.g. cytotoxicity, irritation, or sensitization issues). The Agency recommends performing this type of analysis on a regular basis. 
  • Receiving, reviewing, evaluating, and investigating the complaints (21 CFR 820.198). The draft guidance also provides an approximate list of indications to be monitored by the medical device manufacturers.

The authority also mentions that upon finalizing the guidance, it will conduct periodic reviews of the recommendations, and also of the list of device materials and exclusion characteristics contained therein.

The scope of the guidance covers the medical devices that meet all the criteria described below, namely: 

  • Medical devices that contact skin surfaces only (section 5.2.2(a) of the ISO 10993-1:2018: Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process, 
  • Limited (less or equal to the 25 hours), prolonged (from 24 hours to 30 days), and long-term (more than 30 days) duration of contact, including repeat used devices, and 
  • Composed of materials outlined in the appropriate section of the guidance.

The Agency also provides a list of situations in which the application of the present draft guidance is subject to additional discussion. Such situations include, inter alia, the following ones: 

  • A medical device properly placed on the market is made from the material found to be toxic,
  • A medical device properly placed on the market is made from the material associated with certain adverse clinical findings, 
  • A medical device in question is intended to be marketed in the US and to be used with neonates or pregnant women, 
  • A combination of product or biologically-derived material that could cause adverse biological responses.

Excluded Medical Devices and Materials

The draft guidance also contains a list of specific device materials covered by the scope of the document, including the synthetic polymers and fabrics. At the same time, the Agency also provides a list of excluded medical devices and materials together with the justification of the exclusion. In particular, an exclusion could be applied in case if:

  1. The intact skin-contacting components are made from the materials not included in the appropriate list contained in the guidance (including novel materials and bulk metals), due to the insufficiency of the information related to the biocompatibility risks associated thereto. 
  2. Stored in or containing fluids or creams due to the risks associated with the transferring to such fluids or creams and further absorption by the skin. 
  3. Made using in-situ polymerizing materials, absorbable materials, or hydrogels since their actual characteristics could change depending on the manufacturing process or storing time and conditions. 
  4. Elements contacting breached surfaces, including wounds, due to the increased risk of transferring topical components through such skin.

Summarizing the information provided here above, the FDA draft guidance on certain biocompatibility aspects describes the current thinking of the Agency and its approach to the reduction of unnecessary regulatory burden with regard to the medical devices containing patient contacting materials. A simplified approach could be used only in case of medical devices intended to be used for intact skin and composed of the materials explicitly indicated by the FDA, while in any other case an additional biocompatibility assessment would be required in order to ensure the safety of the patients.

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