Sterilisation Validation for Medical Device Registration in China

1. Key takeaways

Sterilisation and disinfection process studies are one of the nine non-clinical study types in Article 28 of the Medical Device Registration and Filing Measures (SAMR Order No. 47, published 26 August 2021, effective 1 October 2021). Whether a study is needed depends on whether the device is supplied sterile or must be disinfected before use.

• Sterilisation and disinfection are different evidence chains: sterilisation targets verifiable assurance of sterility, disinfection a controlled reduction in microbial load, and their validation depth is not comparable.
• A complete chain has four layers: suitability of product and packaging, process confirmation, routine control, and continued maintenance of the sterile state; missing one weakens the others.
• Article 29 requires method validation, and where statistics apply, the statistical method, sample size basis and acceptance criteria; half-cycle methods, sterility test sample sizes and biological indicator placement all fall under it. Article 31 requires samples to represent the product applied for.
• GRZAN’s assessment: challenges usually arise not from absent validation but from validation on products, packaging or loading that do not match the applied product; how the chain is assembled matters more than any single report.

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 20(1): the registration holder must establish and keep an effective quality management system.

Departmental rules. 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 26: objectively determinable specifications and test methods.
• Article 28: the nine study types include sterilisation and disinfection processes.
• Article 29: method validation required; where statistics apply, the statistical method, sample size basis and acceptance criteria must be specified.
• Article 30: testing against the requirements must pass before trials or application. Article 31: 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.
• Article 121: IVDs follow the separate IVD measures.

The Production Supervision Measures (SAMR Order No. 53, published 10 March 2022, effective 1 May 2022) require in Article 13 a licence decision within twenty working days of acceptance and issue within ten working days of approval; on-site inspection may combine with the registration quality system inspection.

Normative documents. The Production Quality Management Practices (Announcement No. 107 of 2025, published 4 November 2025, effective 1 November 2026) contain fifteen chapters and 132 articles, adding chapters on quality assurance, validation and confirmation, and contract manufacturing; the 2014 announcement No. 64 is repealed. The validation chapter bears directly on sterilisation studies. Announcement No. 121 sets the catalogue; the QMS inspection guide (notice No. 50 of 2022) defines four outcomes; No. 126 governs self-testing; No. 63 clarifies review requirements.

Practical estimate: quantified sterility assurance targets, commonly an SAL of the order of 10⁻⁶, confirmation detail for ethylene oxide, irradiation, moist heat and hydrogen peroxide low-temperature plasma, and indicator selection follow current standards and product guidelines. Requirements differ widely, so search standards before choosing a method.

3. Expert insights

Two chains of different weight. Article 28 lists sterilisation and disinfection together, but the evidence depth differs.

Two route errors are common: over-documenting user disinfection as sterilisation, or under-documenting sterile supply as disinfection. The basis is intended use and initial state of supply.

Confirmation and validation are not interchangeable. Announcement No. 107’s new chapter reinforces the distinction. Confirmation proves that a given process, on this product, in this packaging and loading pattern, reliably reaches the specified sterility assurance level: a one-off proof for a specific combination. Validation and routine control prove each production batch stays controlled, continuously. Reviewers look for confirmation before routine control; a common gap is routine records and sterility tests without confirmation for this combination.

Building the four layers.

The layers are sequential: confirmation is useless if suitability was skipped, for instance where irradiation degrades material performance, and the first three cannot prove sterility over shelf life without the fourth.

Packaging is a sterile barrier system, not an accessory. Sterile packaging must admit the sterilant and exclude microorganisms, so studies are mandatory. Three blocks apply: material suitability; seal confirmation, including strength and integrity parameter windows; and an integrity method that has itself been validated rather than visual inspection. The third is most often simplified, yet inspection cannot decide integrity, and sample size and criteria must be stated (Article 29).

Residues, degradation and compatibility are underestimated. Ethylene oxide requires residue level and toxicity evaluation; irradiation requires degradation and performance study; moist heat requires thermal and moisture tolerance evaluation. All follow one structure: identify, quantify, evaluate, control. Identify the secondary change, quantify residue, degradation product or performance shift, evaluate safety through toxicological or biological assessment, and control it through limits and release criteria. This connects to biological evaluation and the risk file, so that lead should be involved when studies begin.

Representativeness in sterilisation studies. Article 31 raises four issues: a loading pattern or density differing from production, altering sterilant distribution; validation packaging differing from marketed packaging; samples differing in material batch, structure or cleanliness; and no hardest-to-sterilise position or model as the challenge sample. A protocol section on worst-case selection, explaining why the chosen sample, position and load form the hardest case, closes the gap.

4. Practical recommendations

• Decide the route first, sterile supply or user disinfection, which sets evidence depth.
• Build all four layers, flagging any missing layer explicitly.
• Separate confirmation from routine control, confirming this product, packaging and load before setting release criteria.
• Run packaging work in three blocks: material suitability, seal confirmation, validated integrity testing.
• Argue worst-case conditions separately and retain the reasoning (Article 31).
• Handle secondary risks in four steps and write control limits into the technical requirements.
• Link packaging integrity to the end of shelf life.
• After any change of method, packaging or loading, decide between variation and thirty-day filing (Article 79).

5. Verification checklist

• □ Studies completed under Article 28, reasons recorded if not performed?
• □ Supply state identified; documentation depth set?
• □ Layer 1: material compatibility and before-and-after performance?
• □ Layer 1: packaging material suitability for the method?
• □ Layer 2: confirmation for this combination, protocol and report?
• □ Layer 2: biological indicator studies and parameter rationale?
• □ Layer 3: parameters, tolerances, indicator placement, release criteria?
• □ Layer 3: integrity method validated, sample size and criteria?
• □ Layer 3: seal strength and integrity parameter windows?
• □ Layer 4: integrity linked to end of shelf life?
• □ Secondary risks identified, quantified, evaluated, controlled, limits in the requirements?
• □ Validation samples match production in batch, structure, packaging and loading (Article 31)?
• □ Cited standards current; inapplicable ones explained (Article 19)?
• □ After method, packaging or loading changes, 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