Registration Review Guidelines for 10 Medical Devices Including Type I Collagen Cartilage Repair Products Released

Registration review guidelines for 10 medical devices including type I collagen cartilage repair products were released by the Center for Medical Device Evaluation (CMDE) of China's National Medical Products Administration (NMPA) on April 15, 2025. CMDE made the announcement No. 6 of 2025 to standardize the registration review process for the 2 broad areas of 1. orthopedic implants and 2. oral medical devices. These newly released guiding principles define structured technical requirements and classification criteria across key product categories.

Comprehensive Release of Guidance Principles Across Multiple Fields

The 10 registration review guidelines can be allocated to 2 broad areas of 1. orthopedic implants and 2. oral medical devices.

In the field of orthopedic implants, the guiding principles cover several subfields, including type I collagen cartilage repair products, absorbable bone internal fixation implants, metal bone pins, shape-memory alloy rib plates, sternum strapping fixation systems, cranial repair mesh systems, and the evaluation of antibacterial performance of orthopedic implants. In the oral field, the principles address registration reviews for oral repair membranes, bone filling materials for dental implants, and dental resin filling materials (2025 revised edition). The released guidance principles system has the following three major characteristics:

• Field: The orthopedic field has established seven specialized regulations, covering subcategories such as type I collagen cartilage repair products and absorbable bone internal fixation implants. The oral field focuses on regulating three types of products, including bone filling materials for implants and dental resin filling materials.
• Process: A progressive review chain of "naming standards - classification coding - unit division - technical documents" has been established to achieve standardized management of 12 key links in the registration application process.
• Requirements: Taking the "Guiding Principles for the Registration Review of Dental Resin Filling Materials (2025 Revised Edition)" as an example, there are clear stipulations in each key link. In terms of scope of application, it precisely defines dental resin filling materials for filling and repairing various dental defects, excluding dental resin products for luting, caries prevention, lining, or temporary restoration to avoid ambiguity in product scope.

In product naming, strict compliance with relevant regulatory requirements is mandatory. The use of generic names from national or industry standards is required, or naming based on the clinical intended use, main material, and applicable part of the product.

There are clear standards for the division of registration units. Products with different main chemical components, curing mechanisms, or changes in chemical components in the reaction system that lead to alterations in key performance indicators and expected clinical use or purpose, as well as products with different clinical application techniques, should generally be divided into separate registration units. However, products that only differ in color can be declared as the same registration unit.

Key Points of Orthopedic Implant Device Guidance Principles and Impact on Registration

Common Requirements:

• Risk Management and Biological Safety:
  Requirements: Full lifecycle risk management (design, production, use, etc.) must be covered; for animal-derived materials, additional control of virus inactivation and immunogenicity risks is required.
  Impact: The complexity of registration documents increases, requiring more resources for virus inactivation validation, residual detection, and biocompatibility testing (e.g., cytotoxicity, sensitization).
• Technical Requirements and Verification:
  Requirements: Clear physical (size, surface roughness), chemical (material purity), and mechanical performance indicators (tensile strength, fatigue resistance) must be specified; priority should be given to using national or industry standard testing methods.
  Impact: For self-developed testing methods, complete validation evidence (e.g., methodology, reproducibility) must be provided, potentially increasing R&D costs and time.
• Stability and Shelf Life:
  Requirements: Shelf life must be verified through accelerated/real-time aging tests (e.g., material degradation, package barrier properties); transportation stability must be tested under extreme conditions (drop, vibration).
  Impact: Long-term trials (e.g., ultra-high molecular weight polyethylene aging tests) need to be planned in advance, extending the R&D cycle.
• Clinical Evaluation Pathways:
  Requirements: High-risk products (e.g., absorbable implants, antibacterial devices) require clinical trials; some can simplify the process through same-species comparison, but equivalence must be proven.
  Impact: Strict clinical data requirements directly affect the registration cycle and costs (clinical trials are expensive).

Product-Specific Requirements:

• Absorbable Bone Internal Fixation Implants:
  Focus: Degradation performance (synchronization of in vitro/in vivo degradation cycles, degradation product analysis), mechanical strength (e.g., bending strength of bone plates).
  Impact: Long-term animal trials (observation period ≥ 6 months) are needed to verify the synchronization of degradation and bone healing, significantly extending the R&D cycle.
• Antibacterial Orthopedic Implants:
  Focus: Antibacterial substance release characteristics (silver/iodine/antibiotic coatings), in vitro antibacterial tests (bacterial species selection, effective concentration maintenance time).
  Impact: Additional resistance analysis is required, and sterilization processes must avoid deactivation of antibacterial components (e.g., the effect of irradiation on silver ion activity).
• Type I Collagen Cartilage Repair Products:
  Focus: Collagen purity (control of impurities, DNA residues), gelation properties (injectability, mechanical matching).
  Impact: Complex characterization (peptide mapping, immunogenicity) is needed, and large animal models (e.g., pig knee joints) are required for animal trials to verify repair effects.

Recommendations for Response:

• Early Planning: Long-cycle projects such as stability and animal trials should be initiated early (e.g., conducting accelerated aging and real-time aging simultaneously).
• Data Reference: Make full use of same-species comparisons (e.g., data from already marketed titanium mesh plates) to reduce redundant trials.
• Process Optimization: Pay attention to the impact of sterilization/packaging on the properties of antibacterial and absorbable materials (e.g., the interference of ethylene oxide residues with collagen activity).

Key Points of Oral Device Guidance Principles and Impact on Registration

Common Requirements:

• Classification and Naming:
  Requirements: Product names must comply with national standards or clinical use naming rules, and the classification code is uniformly set as Class III (17 oral medical devices).
  Impact: Registrants must strictly follow naming rules to avoid delays in review due to non-standard names.
• Division of Registration Units:
  Requirements: Registration units are divided based on differences in technical principles, raw materials, and processes (e.g., different biological sources or processes require separate units).
  Impact: Similar products may need to be declared in multiple registration units, increasing R&D and documentation preparation costs.
• Technical Requirements and Inspection:
  Requirements: Physical, chemical, and biological performance indicators must be established (e.g., porosity of bone filling materials, curing depth of resin materials, tensile strength of repair membranes).
  Impact: More resources need to be invested in performance verification, and self-developed testing methods must be supported by sufficient evidence.
• Risk Management and Biological Safety:
  Requirements: Full lifecycle risk management is required, and for animal-derived materials, additional control of viral and immunogenic risks is needed.
  Impact: The complexity of biological safety studies increases, especially for virus inactivation and residual detection.
• Stability and Shelf Life:
  Requirements: Shelf life must be verified through accelerated/real-time aging tests, and transportation stability must be tested under extreme conditions.
  Impact: The R&D cycle is extended, and long-term stability trials need to be planned in advance.

Product-Specific Requirements:

• Bone Filling Materials for Implants:
  Focus: Degradation performance (degradation cycle, product analysis) and osteogenic effects (animal trials with a 6-month observation period).
  Impact: Long-term animal trial data are required, increasing time and costs.
• Dental Resin Filling Materials:
  Focus: Curing characteristics (depth, time), wear resistance, and residual monomer control.
  Impact: Formulation and process optimization are needed to meet performance thresholds, and clinical trials may require comparison with similar products.
• Oral Repair Membranes:
  Focus: Structural characteristics (pore size, porosity) and uniformity of degradation are key, and adhesion and support properties need to be verified.
  Impact: Membrane material design must balance mechanical performance and clinical operability, increasing R&D difficulty.

Recommendations for Response:

• Systematic Preparation of Documentation: Cover all dimensions of performance, safety, and effectiveness.
• Focus on Specifics: Pay attention to the biological safety of animal-derived materials and long-term data for degradable products.
• Early Planning of Trials: Long-cycle projects such as stability and animal trials should be initiated as soon as possible.

IV. Impact on Overseas Manufacturers and Recommendations

• Early Planning for Long-Cycle Projects to Avoid Time Risks:
  For time-consuming aspects such as stability testing (e.g., ultra-high molecular weight polyethylene oxidation index testing) and animal trials (large animal models like pig knee joint repair), international companies are advised to initiate "dual-track validation" at an early stage—conducting accelerated aging and real-time aging tests simultaneously, and advancing same-species data comparison and self-built trials in parallel, to avoid registration delays due to insufficient trial periods.
• Precision Response to Special Requirements in Subfields:

— Antibacterial Implants: Attention should be paid to the impact of sterilization processes on antibacterial components (e.g., irradiation may reduce the activity of silver ions), additional resistance analysis should be conducted, and the stability and release characteristics of antibacterial coatings should be ensured to meet clinical expectations.

• — Biological Material Products: For example, type I collagen cartilage repair products, strict control of impurities and DNA residues is required, and complex characterization methods such as peptide mapping and immunogenicity testing should be used to demonstrate the safety and biocompatibility of the materials.
• Leverage Professional Agencies to Enhance Compliance Efficiency:
  The Chinese registration process involves multidisciplinary technical reviews (such as materials science, biology, and clinical data). International companies are advised to collaborate with local professional agencies like Cisema, leveraging their in-depth interpretation experience of guiding principles to optimize registration strategies.

Further Information

To read the original announcement about the submission guidelines for titanium and titanium alloy bone implant medical devices released by China’s Center for Medical Device Evaluation (CMDE), please click here.

If you are a medical device manufacturer with questions about how long it takes or how much it costs to register your titanium implant products for the China market, please contact Cisema.

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