New issue of the FDA Guidance :  Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process"

FDA has developed this guidance document to assist industry in preparing Premarket Applications (PMAs), Humanitarian Device Exceptions (HDEs), Investigational Device Exemption (IDE) Applications, Premarket Notifications (510(k)s), and De Novo requests for medical devices that come into direct contactor indirect contactwith the human body in order to determine the potential for an unacceptable adverse biological response resulting from contact of the component materialsof the device with the body. The purpose of this guidance is to provide further clarification and updated information on the use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" to support applications to FDA. This guidance document also incorporates several considerations, including the use of risk-based approaches to determine if biocompatibility testing is needed, chemical assessment recommendations, and recommendations for biocompatibility test article preparation for devices with submicron or nanotechnology components and for devices made from in situ polymerizing and/or absorbable materials.

FDA first published the guidance in 2016 and revised it previously in 2020. This is the second update of this guidance, published on 8 September, which now includes an attachment that lists certain synthetic polymers and natural fabrics that do not need to meet biocompatibility requirements (Attachment G: Biocompatibility of Certain Devices in Contact with Intact Skin).

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“Many devices have intact skin contacting materials that are made from synthetic polymers and natural fabrics. FDA believes that these materials pose a very low biocompatibility risk because they have a long history of safe use in legally marketed medical devices that contact intact skin.

The policy outlined in this Attachment describes a least burdensome approach for these devices that recommends specific material information to be included in a premarket submission in lieu of biocompatibility testing,” the agency added. “This approach also supports the principles of the ‘3Rs,’ to replace, reduce, and/or refine animal use in testing when feasible.”

According to FDA, the policy is based on its experience with the materials in question and relies on its Quality System Regulations and other policies to track potential biocompatibility issues with products that get to market.

The list of materials that are excluded from typical biocompatibility requirements may be used in medical devices, according to FDA, if the manufacturer has provided certain assurances, such as:

• Purchasing controls (21 CFR 820.50) over material suppliers,
• Production and process controls for manufacturing (21 CFR 820.70). Manufacturing materials that could adversely affect device biocompatibility should be removed or limited to an amount that does not pose toxicity concerns,
• Receiving, in-process, and finished device acceptance (21 CFR 820.80) for component and manufacturing materials,
• Analysis of quality data (21 CFR 820.100(a)(1)), including complaints, to detect quality problems, such as those that may reveal issues of cytotoxicity, irritation, or sensitization. FDA recommends that such an analysis occurs routinely (at least annually), and
• Complaints (21 CFR 820.198) should be received, reviewed, evaluated, and, when necessary, investigated. We recommend that manufacturers process complaints in a uniform and timely manner to look for issues related to cytotoxicity, irritation, or sensitization. Indications of these issues may include: 

• redness (erythema),
• swelling (edema),
• irritation,
• sensitization (delayed Type IV hypersensitivity),
• allergy,
• and immune response or other reactions on the skin where the device has contact.

If manufacturers provide such assurances, the materials would not need to be disclosed in premarket submissions and can include other processing chemicals and additives but cannot include color additives.

In total, FDA listed 24 polymers and three fabrics on the list of materials that do not need to meet typical biocompatibility requirements.

FDA also encouraged external stakeholders to comment in order to suggest the addition or removal of materials in the list, and said that it plans to reassess the list periodically.

The Food and Drug Administration also recommended stakeholders include the generic chemical name, identify FDA medical device product codes, and give a rationale for why the material in question poses a low biocompatibility risk when asking regulators to add the material to its list.

Our Expertise

Biocompatibility is a decisive criterion for the marketing of your medical devices. Changes in the methods used by notified bodies to evaluate technical dossiers have placed this subject at the centre of attention. Biological evaluation is indeed a major part of meeting the general safety and performance requirements.

In the current context, where demand for compliance is strong and urgent, CSDmed is providing manufacturers with its expertise and a methodical approach.

Our biological evaluation experts will help you better understand changes in the standards governing the biological evaluation of your devices. Moreover, our toxicology experts will assist you with your Toxicological Risk Assessment (TRA) according to ISO 10993-17.

CSDmed will support you with a team of specialized experts and consultants who can manage your biological and toxicological evaluation project from implementing the evaluation strategy to writing the final report.

🔗 Contact us and find out how we can help you.