Chapter 3: Non-Clinical Data (非临床资料)

NMPA Reference: Notice 2021-121, Attachment 5, Chapter 3
Document Code: NMPA-CH3
Responsible Party: Manufacturer (CRO supports V&V strategy and documentation)

Requirements Checklist

3.1 Table of Contents

• [ ] All headings and sub-headings with page numbers

3.2 Risk Management Data (产品风险管理资料)

Complete risk management documentation with traceability for each identified hazard:

• [ ] Risk analysis: intended use identification, safety-relevant characteristics, hazard identification, risk estimation per hazard situation
• [ ] Risk evaluation: assessment of each identified hazard situation, determination of risk reduction needs
• [ ] Risk control: risk control measures implemented, verification of effectiveness
• [ ] Residual risk acceptability: evaluation of each individual residual risk
• [ ] Overall risk acceptability: overall benefit-risk assessment confirming acceptability

Key standard: GB/T 42062-2022 (ISO 14971:2019 adoption)

3.3 Essential Principles Checklist (医疗器械安全和性能基本原则清单)

• [ ] Compliance with each applicable requirement from Attachment 9
• [ ] For each applicable principle: method of compliance and evidence documents
• [ ] For non-applicable principles: justification of non-applicability
• [ ] Documents within the dossier: reference to specific dossier location
• [ ] Documents outside the dossier: document name and QMS reference number

The NMPA Essential Principles Checklist (Attachment 9) is broadly equivalent to the EU MDR GSPR (Annex I) but follows a Chinese regulatory structure.

3.4 Product Technical Requirements & Test Reports (产品技术要求及检验报告)

3.4.1 Applicable Standards

• [ ] List all applicable mandatory national (GB) and industry (YY) standards
• [ ] For inapplicable mandatory standards: explanation with supporting evidence
• [ ] Standards compliance checklist

3.4.2 Product Technical Requirement (产品技术要求)

• [ ] Formatted per NMPA Product Technical Requirement regulations
• [ ] Submitted in editable Word format
• [ ] Two physical copies required

The Product Technical Requirement is a unique NMPA document that combines product specifications, test methods, and acceptance criteria into a single regulatory document. No direct EU MDR equivalent.

3.4.3 Test Reports

Acceptable forms (any one of):

• [ ] Self-test report by the applicant, OR
• [ ] Test report from an NMPA-designated testing laboratory

Note: For Class II/III devices, NMPA typically requires testing by designated laboratories, not self-testing.

3.5 Research Data (研究资料)

Provide a non-clinical research summary describing each study, its methodology, and conclusions. Each study should include a study protocol and study report.

3.5.1 Chemical and Physical Performance (化学和物理性能研究)

• [ ] Material characterisation: chemical/material composition
• [ ] Physical and/or mechanical performance indicators: determination basis, design inputs, clinical significance
• [ ] Test standards/methods used with rationale and theoretical basis
• [ ] Flammability/explosion risk: for devices exposed to flammable/explosive substances, demonstrate acceptable risk under normal and single-fault conditions
• [ ] Combination use: for devices used with other medical devices, drugs, or non-medical products -- safety and efficacy data for combination use including interface compatibility, connection types, protocols, minimum performance, and limitations
• [ ] Drug compatibility: for drug-device combinations, compatibility study data
• [ ] Dose-response and energy safety: for therapeutic energy devices, demonstrate safe parameter settings and that non-target tissue is not unacceptably harmed

3.5.2 Electrical System Safety (电气系统安全性研究)

• [ ] Electrical safety studies per applicable standards
• [ ] Mechanical and environmental protection studies
• [ ] Electromagnetic compatibility (EMC) studies
• [ ] Applicable standards compliance documentation

Key standards: GB 9706.1 (IEC 60601-1), GB/T 18268 (IEC 61326 for non-medical EMC)

3.5.3 Radiation Safety (辐射安全研究)

For devices with ionising or non-ionising radiation hazards:

• [ ] Applicable radiation safety standards (general and product-specific)
• [ ] Justification for inapplicable standard clauses
• [ ] Radiation type identification and verification data
• [ ] Demonstrate controllable and adjustable radiation energy, distribution, and key characteristics
• [ ] Radiation dose reduction measures for users, third parties, and patients during transport, storage, installation, and use
• [ ] Misuse prevention methods
• [ ] Installation acceptance testing, performance testing, acceptance criteria, and maintenance procedures (if applicable)

3.5.4 Software Research (软件研究)

3.5.4.1 Software (含软件组件或独立软件)

• [ ] Basic information: software identification, safety classification (serious/medium/minor), architecture and functions, physical topology, operating environment, registration history
• [ ] Development process: development overview, risk management, requirements specification, lifecycle model, V&V activities, traceability analysis, defect management, update history
• [ ] Core function and algorithm mapping to intended use
• [ ] Detail level proportional to safety classification

3.5.4.2 Cybersecurity (网络安全)

For software with electronic data exchange, remote control, or user access:

• [ ] Basic information: software info, data architecture, cybersecurity capabilities, patch strategy, security software
• [ ] Development process: risk management, requirements specification, V&V, traceability, maintenance plan
• [ ] Vulnerability assessment: known vulnerability information and mitigations

3.5.4.3 Off-the-shelf (OTS) Software (现成软件)

• [ ] Software research and cybersecurity data appropriate to OTS type and usage

3.5.4.4 Artificial Intelligence (人工智能)

For devices using deep learning or AI for intended function:

• [ ] Algorithm basic information
• [ ] Data collection methodology
• [ ] Algorithm training process
• [ ] Algorithm performance evaluation
• [ ] Change management plan

3.5.4.5 Interoperability (互操作性)

For devices exchanging and using information via electronic interfaces:

• [ ] Basic information and interface specifications
• [ ] Requirements specification
• [ ] Risk management
• [ ] V&V results
• [ ] Maintenance plan

3.5.4.6 Other Technologies (移动计算/云计算/VR)

• [ ] Basic information, requirements, risk management, V&V, maintenance plan

3.5.5 Biological Characteristics (生物学特性研究)

For devices with direct or indirect patient contact:

• [ ] Material description and contact nature with human body
• [ ] Contaminants and residues from design/manufacturing
• [ ] Leachables, extractables, degradation products, processing residues
• [ ] Packaging materials in direct device contact
• [ ] Physical and/or chemical characterisation (including physical action risks)
• [ ] Biocompatibility evaluation strategy, basis, and methods
• [ ] Evaluation of existing data and results
• [ ] Justification for test selection or exemption
• [ ] Additional data required for complete evaluation
• [ ] Nanoparticle risk: for devices containing, generating, or composed of nanomaterials -- biological risk assessment
• [ ] Absorbable devices: compatibility data between materials/substances and human tissues, cells, body fluids

Key standard: GB/T 16886 series (ISO 10993 adoption)

3.5.6 Biological Source Material Safety (生物源材料的安全性研究)

For devices containing allogeneic, animal-origin, or bioactive substances:

• [ ] Material/substance source description
• [ ] Tissue, cell, and material acquisition, processing, preservation, testing procedures
• [ ] Virus inactivation/removal process and effectiveness validation data
• [ ] Immunogenicity reduction methods and quality control data
• [ ] Supporting safety documentation

3.5.7 Cleaning, Disinfection, Sterilisation (清洁、消毒、灭菌研究)

• [ ] Manufacturer sterilisation: sterilisation method, parameters, SAL level, validation and confirmation data
• [ ] User sterilisation: recommended method and parameters, rationale, validation data; for multi-cycle devices: sterilisation tolerance data
• [ ] User cleaning and disinfection: recommended methods, parameters, rationale, validation data
• [ ] Residual toxicity: for post-sterilisation/disinfection residues -- residue identification, processing methods, study data
• [ ] Non-sterile delivery for user sterilisation: packaging evidence for microbial contamination reduction and sterilisation method compatibility

3.5.8 Animal Studies (动物试验研究)

• [ ] Scientific decision documentation: justification for conducting or not conducting animal studies
• [ ] If conducted: study objectives, animal information, test and control device details, animal numbers, evaluation endpoints, results
• [ ] Design rationale for all study elements

3.5.9 Other Safety and Efficacy Studies

• [ ] Any additional studies demonstrating product safety and efficacy

3.6 Non-Clinical Literature (非临床文献)

• [ ] Bibliography of published non-clinical studies relevant to the device (cadaver studies, biomechanical studies, etc.)
• [ ] Copies of referenced publications (with Chinese translations for foreign-language documents)
• [ ] If no relevant literature found: formal declaration

3.7 Stability Studies (稳定性研究)

3.7.1 Shelf Life (货架有效期)

• [ ] Shelf-life and packaging study data
• [ ] Demonstrate performance maintenance under manufacturer-specified transport and storage conditions
• [ ] For devices with microbial limits: microbial limit compliance data
• [ ] For sterile-delivered devices: sterility maintenance data

3.7.2 In-Use Stability (使用稳定性)

• [ ] Reliability study data for the specified use period or use count
• [ ] Demonstrate performance under normal use, maintenance, and calibration (if applicable)

3.7.3 Transport Stability (运输稳定性)

• [ ] Transport stability and packaging data
• [ ] Demonstrate that transport conditions (vibration, temperature, humidity fluctuations) do not adversely affect device characteristics, performance, integrity, or cleanliness

3.8 Other Data (其他资料)

• [ ] For Class II/III devices exempt from clinical evaluation: comparison with listed exempt products per NMPA Guidance Principles, covering: basic principle, structure, performance, safety, intended use
• [ ] For single-use devices: supporting data proving non-reusability

Comparison with EU MDR

Aspect	NMPA Ch.3	EU MDR Annex II Section 5-6
Risk management	Same ISO 14971 basis	Same ISO 14971 basis
Essential principles	Attachment 9 checklist	Annex I GSPR
Software	6 detailed sub-categories (AI, cyber, OTS, interop, cloud/VR)	Integrated into V&V
Product Technical Req	Unique NMPA document	No equivalent
Testing	Mandatory designated lab testing for Class II/III	NB decides scope
Stability	3 types required (shelf, in-use, transport)	Covered in V&V
Animal studies	Decision justification required	Decision justification required