The National Institutes for Food and Drug Control of NMPA released the draft GB/T 16886.1-2025, “Biological Evaluation of Medical Devices — Part 1: Evaluation and Testing Within a Risk Management Process” on August 21, 2025 for feedback. This draft represents the Chinese adoption of ISO/FDIS 10993-1:2025, aligning with internationally recognized framework for biological safety evaluation of medical devices.
For our comprehensive review of the draft GB/T 16886.1-2025, please click HERE
For key points to navigate the biological evaluation of Class III medical devices, click HERE
The release of this draft highlights the growing global convergence around the ISO 10993 risk-based evaluation model. As regulatory systems align more closely with the updated ISO framework, it becomes increasingly important to understand how biological evaluation is structured in practice—particularly the roles of the Biological Evaluation Plan (BEP) and the Biological Evaluation Report (BER), which form the foundation of regulatory submissions in both China and the United States.
BEP vs. BER
In the context of ISO 10993 biological evaluation, BEP and BER represent two distinct but closely linked stages within the overall assessment process.
The Biological Evaluation Plan (BEP) is a forward-looking document that defines the strategy for demonstrating biocompatibility before any testing begins. It explains how biological risks will be assessed based on device characteristics such as materials, nature and duration of patient contact, and intended clinical use. The BEP also outlines which endpoints are considered relevant—such as cytotoxicity, sensitization, irritation, or systemic toxicity—and provides scientific justification for both selected and waived tests. In addition, it typically includes plans for chemical characterization and toxicological risk assessment, along with details on test methods, laboratories, and timelines. This document is usually prepared early and may be submitted to regulatory authorities such as NMPA or U.S. Food and Drug Administration as part of a preclinical strategy.
By contrast, the Biological Evaluation Report (BER) is retrospective. It compiles all data generated according to the BEP and provides a comprehensive assessment of whether the device meets biological safety requirements. The BER integrates results from biocompatibility testing, chemical characterization (e.g., per ISO 10993-18), and toxicological risk assessment (e.g., per ISO 10993-17), and concludes with an evaluation of residual risks and overall safety. This report is finalized after all testing is completed and is included in regulatory submissions such as FDA 510(k), NMPA registration, or CE marking.
In simple terms, the BEP defines what will be done and why, while the BER documents what was done and whether it was acceptable. A useful analogy is that the BEP functions like a recipe, whereas the BER represents the finished outcome and its evaluation.
NMPA vs. FDA: Regulatory Requirements and Expectations
Although both China and the U.S base their biological evaluation frameworks on the ISO 10993 standards, their regulatory expectations differ in practice. The Chinese NMPA generally adopts a more conservative and test-driven approach, whereas the FDA emphasizes a risk-based, science-driven strategy.
From a regulatory foundation perspective, NMPA requires compliance with the GB/T 16886 series, which is the Chinese equivalent of ISO 10993. Testing is expected to be conducted in GLP-compliant laboratories, and in practice, authorities often expect a relatively comprehensive test package. In contrast, FDA uses ISO 10993-1 as the core framework but supplements it with detailed guidance documents that integrate biological evaluation into a broader risk management process, allowing greater flexibility when justified.
Differences become more apparent in testing expectations. NMPA typically requires broader testing panels and may include additional endpoints such as subchronic toxicity, reproductive toxicity, or multiple implantation studies. FDA, on the other hand, increasingly relies on chemistry and toxicology to refine testing strategies.
FDA’s approach often centers on the following considerations:
- Chemical characterization of materials (extractables and leachables)
- Toxicological risk assessment to evaluate patient exposure
- Device contact type (surface, external communicating, implant)
- Contact duration (limited, prolonged, permanent)
- Existing clinical history or predicate device data
- Material composition and manufacturing changes
- Potential for cumulative or repeated exposure
- Scientific justification for waiving specific endpoints
In contrast, NMPA expectations more commonly include:
- A broader baseline test panel aligned with GB/T 16886
- Inclusion of subchronic toxicity for many device types
- Expanded genotoxicity testing batteries
- Hemocompatibility testing for blood-contacting devices
- Implantation studies where material-tissue interaction is possible
- Reproductive or developmental toxicity in certain cases
- Mandatory GLP compliance for all submitted studies
- Limited acceptance of test waivers without strong, data-driven justification
In terms of risk-based evaluation, both regulators formally align with ISO 10993-1 principles, but their practical implementation differs. NMPA still tends to rely more heavily on predefined testing expectations, while gradually moving toward a more harmonized model. FDA is already deeply integrated with risk management concepts, requiring manufacturers to identify hazards, assess exposure, and justify each testing decision scientifically.
Chemical characterization and toxicological assessment further highlight this contrast. While NMPA accepts chemical characterization data, it generally does not consider it sufficient on its own to replace biological testing. FDA, however, places chemical characterization at the center of its evaluation paradigm. Recent FDA guidance has significantly increased expectations for extractables and leachables analysis, and when combined with a robust toxicological risk assessment, such data can eliminate the need for certain animal studies.
Documentation requirements for BEP and BER are structurally similar but differ in emphasis. NMPA often focuses on strict alignment with GB/T standards and may require repeat testing if data are not locally aligned, whereas FDA emphasizes clarity of scientific rationale and integration across chemistry, toxicology, and biological endpoints.
Overall, the key distinction is that NMPA tends to require broader and more conservative testing, while FDA allows more flexibility through a risk-based, justification-driven approach.
NMPA-Aligned BEP Strategy for Blood-Contacting Devices (BIVAD Example)
For blood-contacting, short-term (≤24 hours) external communicating circulatory system devices such as Biventricular Assist Device (BIVAD), an NMPA-aligned BEP would typically adopt a test-oriented structure. While chemical characterization is increasingly recognized under GB/T 16886.18 (China’s equivalent to ISO 10993-18), it is generally considered supportive rather than determinative. Biological testing remains central to demonstrating safety.
For an externally communicating circulatory system device, Chinese regulators often expect an expanded systemic and hemocompatibility assessment package.
Compared with FDA, NMPA is less likely to waive subchronic toxicity solely based on chemical risk assessment unless strong scientific data and material history are presented. Full GLP compliance is expected, and study reports must clearly reference applicable GB/T standards. Extract conditions must align with Chinese regulatory expectations, and deviations require justification.
A typical NMPA-aligned BEP may include:
- Cytotoxicity (GB/T 16886.5)
- Sensitization testing (GB/T 16886.10)
- Intracutaneous reactivity
- Acute systemic toxicity
- Subacute systemic toxicity (14–28 days)
- Subchronic systemic toxicity (up to 90 days, frequently expected)
- Complete hemocompatibility panel:
- Hemolysis
- Coagulation assays
- Complement activation
- Platelet aggregation
- Thrombosis evaluation
- Pyrogenicity testing (material-mediated)
- Bacterial endotoxin testing
- Genotoxicity battery (Ames + in vitro mammalian assay; in vivo follow-up if triggered)
- Implantation studies for cannula or tissue-contacting components
- Material degradation assessment
- Leachable substance evaluation
- Toxicological evaluation of degradation products
Additional NMPA BEP considerations typically include:
- Clear linkage between identified biological risks and each selected endpoint
- Documentation of laboratory accreditation and GLP status
- Confirmation that test methods strictly follow GB/T versions
- Conservative exposure assumptions
- Evaluation of cumulative systemic effects
- Justification for absence of reproductive toxicity (if applicable)
- Traceability between BEP, test reports, and final BER conclusions
The NMPA-aligned BER must consolidate all biological testing data, chemical analysis results, and toxicological assessments into a structured conclusion demonstrating conformity with GB/T 16886 requirements. While China continues moving toward greater harmonization with ISO 10993 risk-based principles, for high-risk blood-contacting devices such as BIVAD systems, regulators generally expect a robust and comprehensive biological dataset to support registration.