Description
FDA has developed this guidance document to assist industry in preparing Premarket Applications (PMAs), Humanitarian Device Exceptions (HDEs), Investigational Device Applications (IDEs), Premarket Notifications (510(k)s), and De Novo requests for medical devices that come into direct contact or indirect contact with the human body in order to determine the potential for an unacceptable adverse biological response resulting from contact of the component materials of 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, 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, and biocompatibility recommendations when certain materials only contact intact skin.
Scope & Applicability
Product Classes
10FDA intends to assess device cybersecurity based on a number of factors; demonstrate or maintain its safety and effectiveness; ensuring cybersecurity has become essential to FDA’s ability to protect the public health; Cyber-resiliency capabilities for medical devices
Implications of 21 CFR 801.109 for final labeling
Devices requiring pyrogenicity and implantation testing
Devices where in vitro blood damage assessments are used
Evaluated in animal models for safety and thrombogenicity
Devices made from in situ polymerizing and/or absorbable materials
Determining how to prepare for biocompatibility testing
Relevant for consideration as part of a risk assessment
Experience with medical device materials previously reviewed
Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Stakeholders
2Entity responsible for submitting applications under section 524B
Individuals responsible for assessing patients for adverse reactions
Regulatory Context
Attributes
10Use of Medical Device in Final Finished Form; Biocompatibility evaluation of the medical device; The condition of the medical device as it will be used
probability of a specified degree of an adverse reaction occurring
impact the biocompatibility of the device
Limited, prolonged, or long term contact
TTC approach used to determine if quantification without identification is sufficient
Labeling claim for medical devices
Decision criterion (SI) for identifying potential sensitizers
Parameter for extraction testing
GRAS status for food additives
Factor to consider in risk assessment (one-time, constant, or intermittent).
Identified Hazards
Hazards
10Potential risk identified during biocompatibility risk assessment.
potential for a chemical substance or material to cause an adverse biological reaction
prior knowledge from product development, e.g., on leachables
Assessment of toxicity required in a 351(k) BLA
Subset of acute systemic toxicity
Risk of blood clot formation
Risk of febrile reaction
Risk from non-passivated nitinol devices
Possible leachable chemicals or degradation products should be considered
Biological hazards arising from mechanical failure
Related CFR Sections (4)
- 21CFR812.150§ 812.150 Reports.
(a) Investigator reports. An investigator shall prepare and submit the following complete, accurate, and timely reports:Read full regulation →
- 21CFR10.115§ 10.115 Good guidance practices.
(a) What are good guidance practices? Good guidance practices (GGP's) are FDA's policies and procedures for developing, issuing, and using guidance documents.Read full regulation →
- 21CFR801.109§ 801.109 Prescription devices.
A device which, because of any potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use is not safe except under the supervision of a practitioner licensed by law to direct the use of such device, and hence for which “adequate directions for use” canRead full regulation →
- 21CFR3.2§ 3.2 Definitions.
For the purpose of this part:Read full regulation →
Related Warning Letters (10)
- 2025-12-09
CGMP/QSR/Medical Devices/Adulterated
Envoy Medical Inc.
- 2025-11-25
CGMP/QSR/Medical Devices/Adulterated
Hong Qiangxing Shenzhen Electronics Limited
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated
Contec Medical Systems Co., Ltd.
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated/Misbranded
Royal Philips
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated/Misbranded
Qianjiang Kingphar Medical Material Co Ltd.
- 2025-10-21
CGMP/QSR/Medical Devices/Adulterated
LEVO AG
- 2025-10-07
CGMP/QSR/Medical Devices/Adulterated
Technological Medical Advancements LLC
- 2025-09-30
Medical Device Reporting/Misbranded
Insung Medical Co. Ltd.
- 2025-09-23
Medical Device/Adulterated/Misbranded/Lacks PMA and/or 510(k)
The Richline Group, Inc.
- 2025-09-16
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA) Adulterated Device
SeniorLife Technologies, Inc.
See Also (8)
- Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Artificial Intelligence-Enabled Device Software Functions: Lifecycle Management and Marketing Submission Recommendations: Draft Guidance for Industry and Food and Drug Administration Staff (Status: Draft)
- CPG Sec. 280.100 - Stability Requirements - Licensed In Vitro Diagnostic Products (Status: Final)
- Technical Considerations for Demonstrating Reliability of Emergency-Use Injectors Submitted under a BLA, NDA or ANDA: Draft Guidance for Industry and Food and Drug Administration Staff (Status: Draft)
- Bridging for Drug-Device and Biologic-Device Combination Products: Draft Guidance for Industry (Status: Draft)
- Current Good Manufacturing Practice Requirements for Combination Products: Guidance for Industry and FDA Staff (Status: Final)
- Postmarket Management of Cybersecurity in Medical Devices: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Biological Product Deviation Reporting for Licensed Manufacturers of Biological Products Other than Blood and Blood Components (Status: Final)