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General Safety and Performance Requirements (GSPR) under EU Medical Device Regulations: A Core Framework for Ensuring Safety and Effectiveness

The GSPR, outlined in Annex I of the Medical Device Regulation (MDR) and In Vitro Diagnostic Medical Device Regulation (IVDR), serves as the cornerstone for ensuring the safety and effectiveness of medical devices in the EU. Its requirements span multiple critical domains, as detailed below:

I. Core Components of GSPR

GSPR is structured into three chapters in Annex I of the MDR/IVDR:

Chapter 1: General Requirements Based on Risk Management

Medical devices must function as intended without endangering the health or safety of patients, users, or third parties.

Risks must be reduced to an acceptable level without compromising the risk-benefit ratio. For example, design modifications that lower risks but impair device performance or benefits require re-evaluation.

Manufacturers must establish, implement, and maintain a risk management system throughout the device lifecycle (e.g., design, production, post-market surveillance), adhering to ISO 14971.

Chapter 2: Performance, Design, and Manufacturing Requirements

Essential Performance Characteristics: Manufacturers must define core functionalities (e.g., diagnostic sensitivity, therapeutic accuracy) and provide evidence of compliance with standards.

Material Safety: Ensure chemical compliance of materials, avoid hazardous substances, and prioritize risks associated with nanomaterials.

Biocompatibility: Materials in contact with the human body must pass ISO 10993 testing to prevent allergic reactions, irritation, or toxicity.

Performance Validation: Include analytical performance (e.g., sensitivity, specificity) and clinical performance (e.g., diagnostic accuracy), supported by clinical data demonstrating safety and effectiveness.

Chapter 3: Labeling and Instructions for Use

Labels must clearly display indications, usage instructions, intended purposes, warnings, and precautions, complying with EN ISO 18113.

Instructions for self-testing devices must be written in patient-friendly language, including detailed usage steps and risk information.

II. Pathways to GSPR Compliance

Risk Assessment and Management

Manufacturers must identify all potential risks (e.g., biological, chemical, mechanical) and implement control measures (e.g., design improvements, warning labels).

Residual risks must be communicated to users, such as listing foreseeable adverse events in instructions.

Clinical Evaluation and Data Support

Clinical evaluations must rely on peer-reviewed literature, routine diagnostic experience, or other data to demonstrate safety and effectiveness.

High-risk or novel devices require clinical performance studies to provide direct evidence of GSPR compliance.

Technical Documentation and Quality Management Systems

Technical files must include product specifications, performance evaluations, risk management, and clinical assessments, ensuring traceability.

Quality management systems must comply with ISO 13485, covering raw material procurement, production, inspection, packaging, and transportation.

Post-Market Surveillance and Vigilance

Manufacturers must establish systems to monitor adverse events, report to regulatory authorities promptly, and implement corrective actions.

Risk assessments must be updated regularly to ensure ongoing safety and effectiveness throughout the device lifecycle.

III. References for GSPR Compliance

Harmonized Standards

Standards like EN ISO 14971 (risk management) and EN ISO 10993 (biocompatibility) provide detailed guidance for compliance.

The EU Commission publishes a list of harmonized standards on its website. In the absence of such standards, international standards (e.g., ISO, IEC) or national non-harmonized standards may be used.

Common Specifications

Technical or clinical requirements issued for specific devices (e.g., reprocessing of single-use devices, Class D IVDs) supplement the GSPR framework.

IV. Dynamic Updates and Challenges in GSPR

Emerging Domain Requirements

Cybersecurity and Software: Devices reliant on digital connectivity must include long-term update plans to ensure security is integrated from the design phase.

Environmental Impact: GSPR 13–14 require manufacturers to demonstrate the long-term environmental safety of devices and their components.

AI/ML Devices: Algorithm consistency, decision transparency, and post-deployment bias or safety risks must be validated.

Strategies for Compliance

Develop real-time matrices linking GSPR requirements to technical documentation.

Integrate design, clinical, regulatory, and quality teams early, using automation tools to identify gaps.

Regularly review documentation to align with the latest guidance (e.g., 2025 MDR updates).

V. Significance of GSPR

GSPR is mandatory for obtaining the CE mark and permeates the entire registration process. Compliance directly impacts patient safety, market access, and corporate reputation. Manufacturers must adopt a risk-based approach, leveraging clinical data and standards to build a lifecycle management system capable of addressing regulatory challenges and fostering innovation.