TX Q&A

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.

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.

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.

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.

In such cases, the original registered product can be used as the same type of product to complete the clinical evaluation. The comparison focuses mainly on whether there are differences between the product being registered and the original registered product. If there are no differences, the clinical data that can be provided includes pre-market and post-market clinical data of the product, including post-market clinical experience data such as adverse events.

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.

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.

The analytical performance of in vitro diagnostic reagents includes accuracy, precision, detection limit, specificity, and other aspects. It requires the inclusion of samples from different sources, types, concentrations, and other characteristics to fully evaluate the product's performance. Therefore, the reuse of samples should be avoided as much as possible during the evaluation process of these analytical performances.

According to the management by the National Institutes for Food and Drug Control (NIFDC) of national standards and reference materials for in vitro diagnostic reagents, the batch number of these materials is composed of a "product code (6 digits) + batch number (6 digits)" and is publicly available on the NIFDC official website for inquiry. Updates to national standards and reference materials include two scenarios: "batch replacement" and "generation change." The difference is that "batch replacement" involves the preparation of a new batch to ensure the supply of national standards and reference materials without any change in their setup, value, performance acceptance criteria, or product code—only the batch number changes. A "generation change," however, indicates a comprehensive change in the national standards or reference materials, possibly altering their setup, value, or performance acceptance criteria, with both product code and batch number changing. If an in vitro diagnostic reagent product had previously submitted an inspection report meeting the requirements of the national standards or reference materials and was approved, and if there is a "generation change" update to these standards or materials, the registrant must provide a new inspection report demonstrating compliance with the updated national standards or reference materials at the next renewal of registration. If there is only a "batch replacement" update, the registrant does not need to submit a new inspection report for compliance with the post-update national standards or reference materials at the next renewal, but must describe in the registration documentation how the product continues to meet the requirements of the national standards or reference materials.

It is necessary to first clarify the heat treatment methods and parameters for the product, and to evaluate and verify the suitability of these heat treatment methods. It is also important to establish the basis for determining heat treatment parameters (including heating time, holding temperature, and holding time) and the criteria for the acceptability of the results after heat treatment.