Issues to consider in the disinfection and sterilization documentation for active medical devices with numerous accessories
For active medical devices that come with numerous accessories, it is advisable to submit disinfection and sterilization documentation in a list format following the structure of the application form. This list should include the names of the accessories, disinfection/sterilization methods, whether they are for single use or reusable, and whether sterilization is performed by the manufacturer or the end user. Manufacturers who perform sterilization should clearly specify the sterilization process (methods and parameters) and the Sterility Assurance Level (SAL), and provide a sterilization validation report. For end-user sterilization, it is important to specify the recommended sterilization process (methods and parameters) and the basis for determining the recommended sterilization method. For products that can withstand two or more sterilizations, research data on the tolerance of the recommended sterilization method for the product should be provided. If the sterilization method used is likely to leave residues, it is necessary to clearly define the information about the residues and the methods used to handle them, and provide research data. For end-user disinfection, the recommended disinfection process (methods and parameters) and the basis for determining the recommended disinfection method should be clearly specified.
When can procalcitonin test reagents be exempted from clinical trials?
Procalcitonin test reagents are used for the in vitro quantitative determination of procalcitonin in human serum or plasma samples. These reagents are listed in the "Catalogue of In Vitro Diagnostic Reagents Exempt from Clinical Trials," where the intended use is specified for the detection of procalcitonin (PCT) content in human samples, primarily for the auxiliary diagnosis of bacterial infectious diseases. If an applicant declares the use of procalcitonin test reagents for the auxiliary diagnosis of bacterial infections, including assisting in diagnosing infections of varying degrees, they can apply under the exemption from clinical trials pathway. If the applicant declares other intended uses for the procalcitonin test reagents, these do not fall within the scope of the exemption catalogue, and clinical trials must be conducted to confirm the claimed intended uses.
Do medical devices of animal origin need to undergo laboratory validation of their virus inactivation processes to evaluate the effectiveness of the virus inactivation?
According to the "Guidance for Technical Review of Medical Device Registration of Animal Origin" (2017 revised edition), the registration application for medical devices of animal origin must include research data that contains descriptions of the processes for inactivating and removing viruses and/or infectious agents during production, as well as data or relevant information validating the effectiveness of these processes. Validation data can be obtained through laboratory verification, from suppliers of animal-derived materials, or by evaluating the effectiveness of virus inactivation through literature or historical data. If the submitted validation data is not based on verification obtained from the product itself, an analysis and argument for applicability must be conducted.
What other types of injectable fillers, besides hyaluronic acid and collagen, have been approved for use? What materials are they made of? What are the differences?
Currently, in addition to fillers primarily composed of sodium hyaluronate or collagen, the following types of injectable fillers have been approved: 1. Fillers composed of sodium hyaluronate and hydroxypropyl methylcellulose: - Medical hydroxypropyl methylcellulose-sodium hyaluronate solution: A sterile gel solution composed of hydroxypropyl methylcellulose, sodium hyaluronate, and balanced salt solution. It is used for deep dermal to superficial subcutaneous injection to correct moderate to severe forehead wrinkles and nasolabial folds. - Medical sodium hyaluronate-hydroxypropyl methylcellulose gel: Mainly composed of cross-linked sodium hyaluronate particles, hydroxypropyl methylcellulose, phosphate sodium chloride buffer solution, and water for injection. It is used for subcutaneous shallow to deep filling to correct moderate to severe forehead wrinkles and nasolabial folds. 2. Fillers made of absorbable polyester materials formed into microspheres and supplemented with excipients: - Poly-l-lactic acid facial filler: This product consists of poly-l-lactic acid microspheres, mannitol, and sodium carboxymethylcellulose in a lyophilized powder, which must be reconstituted with 0.9% sodium chloride injection solution into a suspension before use. It is suitable for deep dermal injection to correct moderate to severe nasolabial folds. - Injectable poly-caprolactone microsphere facial filler: Composed of synthetically produced poly-caprolactone (PCL) microspheres, glycerin, hydroxymethylcellulose, and phosphate buffer solution. It is used for subcutaneous implantation to correct moderate to severe nasolabial folds. 3. Cross-linked sodium hyaluronate gel containing microspheres of L-lactic acid-ethylene glycol copolymer: Mainly composed of cross-linked sodium hyaluronate, L-lactic acid-ethylene glycol copolymer microspheres, lidocaine hydrochloride, and a phosphate buffer system. It is suitable for deep dermal, superficial, and deep subcutaneous injection to correct moderate and severe nasolabial folds. 4. Fillers containing non-degradable components (i.e., permanent fillers): - Collagen and PMMA subcutaneous implant system: This product is a collagen suspension containing polymethylmethacrylate (PMMA) microspheres, with a trace amount of lidocaine. The collagen is sourced from bovine skin in Australia. The 0.1ml size is for allergy testing with a test needle, composed of bovine collagen solution. It is used for deep dermal injections to correct nasolabial folds or for subperiosteal implantation for rhinoplasty (nasal bone section). The PMMA component is non-degradable. - Medical sodium hyaluronate-hydroxypropyl methylcellulose gel containing polyvinyl alcohol microspheres: Mainly composed of sodium hyaluronate, hydroxypropyl methylcellulose, polyvinyl alcohol microspheres, and balanced salt solution. It is used for deep dermal and superficial subcutaneous injection to correct moderate to severe forehead wrinkles and nasolabial folds. The polyvinyl alcohol component is non-degradable.
What is collagen? What is recombinant collagen? What are the approved collagen products for medical cosmetic purposes, and how do they work?
Collagen, commonly referred to as just collagen, is the main structural protein in human tissues and organs, playing a crucial role in tissue repair. There are currently 28 known types of collagen, accounting for about 30-40% of the total protein in the human body, making it one of the most important structural materials in the body. Collagen materials are widely used clinically for the repair of human skin, oral mucosa, dura mater, and other tissues, as well as in medical aesthetics. The collagen products on the medical device market both domestically and internationally are mainly prepared from animal tissues and allogeneic tissues (such as skin and placenta), and there are also recombinant collagens. Recombinant collagen is prepared using DNA recombinant technology, allowing the amino acid sequence to be designed and improved according to needs, such as recombinant humanized collagen whose repeating units have the same amino acid sequence in specific functional areas as human collagen. This method of preparation allows for customized synthesis, not only synthesizing different types of collagen but also selecting and customizing combinations of specific functional areas on different types of collagen molecules as needed. In the field of medical aesthetics, collagen is used as a tissue filler injected into facial tissues, which serves to support and fill the tissue, thereby helping to correct wrinkles. Currently approved filler products include collagen implants, lidocaine-containing collagen implants, medical collagen fillers, and lyophilized fibers of recombinant type III humanized collagen. Some products are used to correct nasolabial folds, while others are used to correct dynamic wrinkles on the forehead. Additionally, some collagen products are made into dressings for medical aesthetic purposes, such as for post-laser skin surgery wound repair. Approved products in this category include collagen dressing materials.
What is hyaluronic acid? What are the approved products of hyaluronic acid for medical cosmetic purposes, and how do they work?
Hyaluronic acid, also known as hyaluronan or by its nickname "glass acid," is a linear polysaccharide composed of repeating disaccharide units of N-acetylglucosamine and glucuronic acid. The term "hyaluronic acid" comes from its common name in Taiwan. It is a component of the extracellular matrix, typically present in the form of its sodium salt (sodium hyaluronate), and is widely distributed in human tissues such as joint cartilage. Hyaluronic acid was first discovered in the eye of a cow, and it was initially mass-produced using extraction from rooster combs, but now it is primarily produced through microbial fermentation. Depending on the clinical application, medical sodium hyaluronate products are regulated either as medical devices or as pharmaceuticals. According to the "Announcement on the Management Category of Medical Sodium Hyaluronate Products" (Notice No. 81 of 2009 by the National Food and Drug Administration), these products are classified based on their intended use. As per the 2017 "Medical Device Classification Catalogue," sodium hyaluronate products used for tissue volume augmentation fall under the primary category "09 Plastic and General Surgical Implants" and the secondary category "02 Plastic Surgery Injectable Fillers," and are managed as Class III medical devices. Products not intended for volume augmentation are classified based on their ingredients and primary mechanism of action to determine if they are considered medical devices. In the field of medical aesthetics, sodium hyaluronate is used as a dermal filler injected into facial tissues to provide support and volume, thereby helping to correct wrinkles. After injection, sodium hyaluronate is eventually broken down in the body. To prolong its degradation, it is often chemically cross-linked to form a more stable, mesh-like structure. The duration of its persistence in the body depends on the degree of cross-linking, particle size, the amount and site of injection, and individual differences. Currently, the main approved products containing sodium hyaluronate as an active ingredient are "Cross-Linked Hyaluronic Acid Gel for Injection" and "Modified Hyaluronic Acid Gel for Injection." There are also approved non-cross-linked sodium hyaluronate products such as "Sodium Hyaluronate Composite Solution for Injection," intended for correcting superficial wrinkles. Additionally, some approved filler products contain hyaluronic acid as a secondary ingredient, including medical hydroxypropyl methylcellulose-sodium hyaluronate solution, medical sodium hyaluronate-hydroxypropyl methylcellulose gel, medical polyvinyl alcohol gel microsphere-containing sodium hyaluronate-hydroxypropyl methylcellulose gel, and cross-linked sodium hyaluronate gel containing polylactic acid-ethylene glycol copolymer microspheres. Most of these products are used to correct moderate to severe nasolabial folds, with a few approved for correcting forehead wrinkles, very few for lip augmentation, rhinoplasty, mid-face injections, and correcting wrinkles on the neck or hands. Due to its strong hygroscopic properties, the medical aesthetics industry also utilizes hyaluronic acid's "moisture-locking" function. For instance, "skin boosters" are treatments where a solution primarily composed of hyaluronic acid is injected into the superficial dermis to improve skin condition, although there are currently no skin booster implants approved as medical devices. There are approved sterile injection needles for skin boosters (managed as Class III medical devices) and electronic injectors on the market.
What is Thermage? How does Thermage work, and what effects can it have? What are the risks?
Thermage, transliterated from the English "Thermage," was originally a brand name under Thermage, Inc. (later Solta Medical, Inc.), which produced a series of radiofrequency cosmetic devices, such as the Thermage CPT System. After being introduced in China, the term "Thermage" became widely known through extensive promotion by its agents and distributors, and it even became synonymous with radiofrequency cosmetic devices in the beauty industry. The working principle of radiofrequency cosmetic devices involves using a specific frequency of electric current that passes directly through human tissue to generate a thermal effect. This heats the skin and subcutaneous tissue to promote the regeneration of collagen, thereby aiming to reduce skin wrinkles. The principle is similar to that of "high-frequency electrosurgical units" used in surgery, usually with a similar or slightly higher frequency. The treatment electrodes are enlarged to reduce the current density, thus keeping the tissue temperature rise within an acceptable range, protecting normal tissues from damage while stimulating collagen regeneration. Some radiofrequency devices use smaller contact area treatment electrodes (often array-type microelectrodes), creating higher current density at the contact points on the skin, causing skin damage and peeling (similar to the effect of fractional CO2 laser treatment), which promotes skin renewal to improve symptoms like wrinkles and acne scars. Another type of device incorporates radiofrequency microneedles with array electrodes, allowing direct application of radiofrequency energy to deeper tissues like the dermis for better treatment outcomes. Conventional radiofrequency cosmetic devices use bipolar or multipolar methods, focusing energy more on the skin and superficial layers. Using monopolar radiofrequency or adding additional modulated pulses can potentially target deeper fat tissues, aiming for fat reduction effects. Although products for such purposes have been submitted for registration, they have not been approved. Approved uses of radiofrequency devices are limited to skin wrinkles and atrophic scars. Since radiofrequency devices fundamentally use electric current's thermal effect on the body, they must comply with relevant general and specific electrical safety standards to avoid potential harm like electric shock or irritation. Based on different current frequencies and tissue characteristics, the depth and range of current flow through the body vary, potentially causing different levels of heat and temperature rise, with a risk of tissue burns. The depth of action is usually not very deep, focusing mainly on the skin and superficial tissues. To increase patient tolerance, these products often employ surface cooling or topical anesthesia to enhance treatment effectiveness, but this also carries a higher risk of thermal tissue damage. For safety, patients must be conscious and aware during treatment, and treatments under deep or general anesthesia are not allowed. Besides common adverse events like skin redness and tissue burns, invasive or peeling treatments can also cause hyperpigmentation risks (similar to laser treatments). Using uncertified products, exceeding intended use, or improper operation can significantly increase the likelihood of electric shock and burns.
During clinical trials of in vitro diagnostic reagents, what should be considered regarding samples?
In clinical trials, when testing clinical samples of the type specified in the user manual, attention should be paid to the conformity of technical aspects such as sample collection, sample storage conditions, sample storage duration, and sample processing methods. Claims made in the reagent instructions should be supported by preclinical studies, and the requirements in the instructions for the test reagents, as well as comparative and review reagents, should also be considered. For example, during clinical trials of nucleic acid testing reagents, it is important to ensure that: the sample collection method complies with the instructions; the sample storage time is within the claimed effective period for the samples; clinical trials should use original clinical samples, and extracted DNA or RNA nucleic acids are not considered original samples; nucleic acid extraction/purification reagents and sample preservation solutions (if applicable) claimed in the product instructions of the test and comparative reagents should be used; if the product instructions have specific requirements for the purity and concentration of extracted nucleic acids, these should meet the relevant requirements specified in each product's instructions.
If a product is made from materials that comply with Appendix B of YY 0341.1 for clinical use, can biological data be exempted from submission during registration?
Biological evaluations cannot be exempted. However, equivalence comparisons can be used to demonstrate that the product being registered has the same biocompatibility as an already marketed product, thereby potentially reducing or exempting the biological tests for the registered product. For materials that comply with Appendix B of YY 0341.1, equivalence comparisons are still required. For instance, it must be demonstrated whether the manufacturing process introduces new biological risks, and whether both products have the same manufacturing processes (processing, sterilization, packaging, etc.), as the manufacturing process can also introduce new harmful substances (residues of sterilants, processing aids, mold release agents, etc.). If it is evaluated that the manufacturing process does not introduce new biological risks, then the biological tests might be considered exempt.
If a medical device containing software adds a new clinical function and the registrant considers this change to be minor, can it be omitted from the release version?
No. Changes in clinical functionality should be considered significant software updates. When the software version naming rules set by the manufacturer do not clearly distinguish between major and minor software updates, follow the principle of higher risk. In software release versions within China, changes should be reflected. For example, if the manufacturer's software version naming rule is X.Y.Z, where X indicates a major update, Y a minor update, and Z a correction; and the clinical functionality change is reflected in the Y field, then the software release version should be determined as X.Y.