Master file registration for medical devices in China is conducted in accordance with the "Announcement on Medical Device Master File Registration" and related regulatory provisions. It involves confidential technical information about the composition and manufacturing processes of medical device raw materials, which can be registered by the suppliers of these raw materials.

The registration dossier includes descriptions of raw material composition, physicochemical performance research data, biological evaluation data, and toxicological risk analysis data. These documents are submitted by the raw material owners to the medical device technical review authorities and are used to authorize medical device registration applicants to reference them as part of their registration documentation. The establishment of the master file system not only facilitates the selection of raw materials and key components by medical device manufacturers but also simplifies the registration process.

Master file registration is applicable for the registration, modification, and clinical trial approvals of imported Class II and Class III medical devices, as well as domestic Class III medical devices (including in vitro diagnostic reagents) within China.

Testing Items Involved in Master File Registration

The testing items required for master file registration vary depending on the medical device raw materials involved. Below are some common raw materials and their associated testing items compiled by CIRS Testing:

Animal-Origin Collagen

• Biocompatibility: Cytotoxicity, irritation response, sensitization, pyrogenicity, genotoxicity, subcutaneous implantation, immunogenicity, systemic toxicity, and carcinogenicity.
• Physicochemical Properties: Appearance, visible impurities, solubility, moisture ash residue, pH value, osmotic pressure molarity, dynamic viscosity, thermal stability, loading and variability, melting point.
• Identification: Peptide mapping, terminal amino acid sequence, molecular weight, isoelectric point.
• Purity: Purity testing by electrophoresis or high-performance liquid chromatography.
• Impurities, Contaminants, and Additives: Protein impurity analysis, residual amounts of exogenous DNA, residual antibiotic content/activity, heavy metals and trace elements content.
• Safety Tests: Sterility, bacterial endotoxin, and microbial limits.

PCL (Polycaprolactone)

• Appearance
• Physicochemical Indices: Intrinsic viscosity, moisture content, density, melt flow rate, melting point, molecular weight distribution, biodegradability.
• Biocompatibility: Cytotoxicity, sensitization, irritation or intradermal reaction, material-mediated pyrogenicity, acute systemic toxicity, subacute toxicity, implantation response, and genotoxicity tests.
• Shelf Life and Packaging Transportation: Verification according to guidelines such as "Guidance on Shelf Life Registration of Non-Active Implantable Medical Devices", GB/T 19633 series, YY/T 0681 series.

PDRN (Polydeoxyribonucleotide)

• Physicochemical Performance: Appearance, visible impurities, loss on drying, residual other chemical agents, transdermal testing.
• Biological Functionality: Cell proliferation, differentiation, adhesiveness, migration or motility tests.
• Biocompatibility: Cytotoxicity, sensitization, irritation or intradermal reaction, material-mediated pyrogenicity, acute systemic toxicity, subacute toxicity, implantation response, and genotoxicity tests.
• Sterilization Validation: Validation of sterilization methods such as steam, ethylene oxide, and radiation.
• Shelf Life and Packaging Transportation: Verification according to guidelines such as "Guidance on Shelf Life Registration of Non-Active Implantable Medical Devices", GB/T 19633 series, YY/T 0681 series.
• Pharmacological Performance Studies: Pharmacokinetics, pharmacodynamics.
• Animal Source Immunogenicity Data: Virus inactivation/removal process validation, long-term supply agreements with designated animal breeding units, qualification certificates of designated breeding units.

PEKK (Polyetheretherketone)

• Physicochemical Performance: Tensile strength, elongation at break, flexural strength, flexural modulus, cantilever beam notch impact strength, density, viscosity, glass transition temperature, melting peak temperature, load deformation temperature, heavy metal content.
• Identification: Identification through infrared spectroscopy.
• Biocompatibility: Cytotoxicity, sensitization, irritation or intradermal reaction, material-mediated pyrogenicity, acute systemic toxicity, subacute toxicity, subchronic toxicity, chronic toxicity, implantation response, genotoxicity, and carcinogenicity tests.
• Sterilization Validation: Validation of sterilization methods such as steam, ethylene oxide, and radiation.
• Shelf Life and Packaging Transportation: Verification according to guidelines such as "Guidance on Shelf Life Registration of Non-Active Implantable Medical Devices", GB/T 19633 series, YY/T 0681 series.

PLLA (Poly-L-lactic Acid)

• Physicochemical Performance: Monomer residue, solvent residue, catalyst residue (optional), water residue (optional), heavy metal content (measured as lead), specific optical rotation.
• Physical Properties: Appearance, density, thermal/crystalline properties, melting point, molar mass (determined by intrinsic viscosity).
• Identification: Identification using infrared spectroscopy, ^1H-NMR, or ^13C-NMR spectroscopy.
• Biocompatibility: Cytotoxicity, sensitization, irritation or intradermal reaction, material-mediated pyrogenicity, acute systemic toxicity, subacute toxicity, implantation response, and genotoxicity tests.
• Shelf Life and Packaging Transportation: Verification according to guidelines such as "Guidance on Shelf Life Registration of Non-Active Implantable Medical Devices", GB/T 19633 series, YY/T 0681 series.

Silicone Rubber

• Physicochemical Performance: Appearance, loss on drying, trace element determination (lead, cadmium, arsenic, chromium, iron, etc.), leachables requirements (solution appearance, evaporation residue, pH, catalyst residue, reductant substances, UV absorption, heavy metals).
• Identification: Testing with infrared spectrophotometry to obtain the infrared spectrum of silicone rubber.
• Biocompatibility: Cytotoxicity, sensitization, irritation or intradermal reaction, material-mediated pyrogenicity, acute systemic toxicity, subacute toxicity, subchronic toxicity, chronic toxicity, implantation response, genotoxicity, and carcinogenicity tests.
• Sterilization Validation: Validation of sterilization methods such as steam, ethylene oxide, and radiation.
• Shelf Life and Packaging Transportation: Verification according to guidelines such as "Guidance on Shelf Life Registration of Non-Active Implantable Medical Devices", GB/T 19633 series, YY/T 0681 series.

Additional materials like silk fibroin, hydroxyapatite (HA), recombinant collagen, and polycarbonate (PC) also have specific requirements for physicochemical properties, biocompatibility, sterilization, and shelf life during master file registration.

Master File Registration Testing Services

• Raw Material Composition Analysis: Identification of material components through spectroscopic analysis.
• Physicochemical Performance Testing: Comprehensive testing of raw materials' physicochemical properties in accordance with domestic and international regulations and standards.
• Biocompatibility Assessment: Biological evaluation of raw materials using internationally recognized biocompatibility testing methods.
• Sterilization Validation: Providing validation services for various sterilization methods to ensure the stability of material performance post-sterilization.
• Shelf Life and Packaging Transportation Validation: Simulating actual use conditions to assess the stability of raw materials and the reliability of packaging and transportation.

If you need any assistance or have any questions, please get in touch with us via test@cirs-group.com.