Biological Evaluation Requirements for Medical Devices in China

1. Key takeaways

Biological characteristics studies and biological source material safety studies are two of the nine non-clinical study types listed in Article 28 of the Medical Device Registration and Filing Measures (SAMR Order No. 47, published 26 August 2021, effective 1 October 2021). The GB/T 16886 series and the ISO 10993 series apply.

• Biological evaluation is a judgement followed by a selection: establish contact category and duration, decide which endpoints need evaluation, then decide which tests to run and which may be exempted.
• An exemption argument is not an omission but a substitution with stronger evidence. Material characterisation data, existing biological data and clinical use history are the three sources.
• Article 29 requires method validation, and where statistics apply, the statistical method, sample size basis and acceptance criteria. Article 31 requires samples to represent the product applied for, including sterilisation state, ageing state and material batch.
• GRZAN’s assessment: most corrections arise where tests were run but the argument was never written. A test report is evidence; the evaluation report is the conclusion, and the latter is what reviewers actually read.

2. Legal basis

Administrative regulation. The Regulation (State Council Order No. 739, published 9 February 2021, effective 1 June 2021) provides:

• Article 5: supervision follows risk management, whole-process control, scientific oversight and social co-governance.
• Article 14: seven categories of materials, including risk analysis, technical requirements, test report and clinical evaluation.
• Article 25: two routes for clinical evaluation.

Departmental rule. Order No. 47 specifies:

• Article 19: applicable mandatory standards met; inapplicable ones explained with materials.
• Article 24: risk management runs across the whole life cycle.
• Article 28: the nine study types include biological characteristics and biological source material safety.
• Article 29: method validation required; where statistics apply, the statistical method, sample size basis and acceptance criteria must be specified.
• Article 31: test samples must represent the product applied for.
• Article 41: deficiencies notified once in full, answered once within one year, otherwise review terminates with a refusal.
• Article 79: substantive changes require variation registration; other changes are filed within thirty days.

Standards and normative documents. The GB/T 16886 series, the national standards for biological evaluation of medical devices, and the ISO 10993 series form the framework. Announcement No. 121 of 2021 sets the dossier catalogue; No. 126 governs self-testing, with the inspection guide of 16 September 2025; the QMS inspection guide (notice No. 50 of 2022) covers on-site inspection; No. 63 of 2025, Part Four, clarifies review requirements.

Practical estimate: the part numbers, year designations and endpoint tables of GB/T 16886 and ISO 10993, and the contact category and duration bands, follow the versions in force; parts cross-reference each other, so endpoint selection may shift after revision. Verify versions before locking the plan.

3. Expert insights

Applicability, then endpoints, then testing. The correct order has three steps, not one.

Step two is the one most often missing. The standard offers a framework of endpoints to consider; the applicant must state why these endpoints were chosen and the others were not, judged against material, contact nature, contact duration, processing and leachable levels.

Three tiers of exemption evidence. Exemption is not omission. Evidence ranks from strongest to weakest.

Tier one is strongest but hardest, because identical grades often sit alongside different processing aids, cleaning or sterilisation, breaking the chain. Tier two is the route with growing acceptance, provided characterisation is solid. Tier three normally supplements rather than stands alone.

Material characterisation is the technical precondition. Whether existing data are relied on or toxicology replaces testing, composition and leachable levels must be known. Characterisation covers four checkable dimensions: composition and grade; processing aids and residual monomers; the leachable profile after sterilisation and cleaning; and identification and quantification of degradation products. Missing any one leaves toxicological assessment without inputs. Characterisation should precede testing rather than run in parallel, because endpoints set after the data arrive often remove unnecessary tests.

Method validation and statistics. Article 29 reaches biological evaluation in three places. Validation asks whether the test suits the matrix, whether extraction conditions (medium, temperature, time, ratio) are justified, whether positive and negative controls are appropriate, and whether any deviation from a standard method is explained. Statistics covers scored endpoints such as irritation and sensitisation, where the method, sample size basis and criteria must be fixed in the protocol. Criteria must state where each pass limit comes from. Much controversy concerns extraction conditions, since solvent, temperature and time change the leachable profile and hence the conclusion; extraction must correspond to clinical use and be justified.

Four break points in sample representativeness. Under Article 31: samples not subjected to final sterilisation while the marketed product is sterile; fresh samples with no consideration of end-of-shelf-life change; samples from development batches differing in material lot or supplier from production; and samples of raw material plaques rather than the finished device or a representative part. A sample status table with one row per report, recording sterilisation, ageing, batch and form against the marketed state, lets a representativeness question be answered at correction stage in one pass.

Links to risk management and clinical evaluation. Biological evaluation connects in two directions. Downward, biological hazards, risk estimation and control measures need entries in the risk management file, with effectiveness supported by biological data. Upward, in an exemption or equivalence route, biological safety is a major part of showing no significant difference from the comparator; in a clinical trial route it underpins subject safety. The conclusion should answer each biological hazard identified in the risk file rather than simply list results.

4. Practical recommendations

• Verify the current editions of the relevant GB/T 16886 and ISO 10993 parts before locking the plan.
• Work in three steps: applicability, endpoint justification, then testing and exemption.
• Complete material characterisation before biological testing and set endpoints afterwards.
• Organise exemption arguments in three tiers, stating equivalence and comparability at each.
• Justify extraction medium, temperature, time and ratio against clinical use.
• Fix the statistical design in advance for scored endpoints (Article 29).
• Answer each risk management hazard item in the evaluation conclusion.
• Bring material changes into change monitoring and reassess the conclusion, deciding between variation and thirty-day filing.

5. Verification checklist

• □ Biological and biological source material studies completed before applying (Article 28)?
• □ Applicability judged, with contact category and duration recorded?
• □ Reasons given for including and excluding each endpoint?
• □ Four characterisation elements present: composition, processing aids, leachables, degradation products?
• □ Exemption argument organised in three tiers with complete equivalence reasoning?
• □ Method validation done, deviations from standard methods explained (Article 29)?
• □ Extraction conditions justified against clinical use?
• □ Where statistics apply, method, sample size basis and criteria fixed?
• □ Sample sterilisation, ageing, batch and form consistent with the marketed product (Article 31)?
• □ Cited GB/T 16886 and ISO 10993 parts current?
• □ Evaluation conclusion answers each biological hazard in the risk file?
• □ Self-tested biological items meet Announcement No. 126?
• □ Protocol, raw records, statistical output and report archived?
• □ Conclusion reassessed after material or process change, route decided (Article 79)?

Regulatory information verified as at 29 October 2026. Legal texts follow the versions published by NMPA, SAMR and gov.cn and must be rechecked after amendment or repeal. Time limits, fees and catalogue scope reflect the official position on that date; content marked practical estimate has no legal effect.

How GRZAN can help. GRZAN provides medical device and IVD registration, quality system, authorised representative and local testing support for the Chinese market. Our team prepares NMPA-compliant dossiers, coordinates typetesting and clinical evaluation documents, and supports post-market vigilance obligations. Business enquiries: info@grzanglobal.com