Should material properties be included in the technical requirements for medical device products?
The answer is that, in principle, material properties are not included as performance indicators in the technical requirements of products. This includes, but is not limited to, the chemical composition, microstructure, and internal quality of metal materials; infrared spectra of polymer materials; and the chemical composition, impurity element content, thermal conductivity, and crystalline phase content of ceramic materials. For material characterization information that is truly related to product safety, it can be specified in an appendix to the technical requirements.
Do absorbable medical device products necessarily require in vivo metabolism studies?
The raw materials of absorbable products can be absorbed by the human body, which may pose safety risks regarding their metabolism inside the body. However, for most established materials such as sodium hyaluronate, animal collagen, chitosan, starch, and polylactic acid, there is abundant research literature available, and their metabolic pathways are relatively fixed. The effects of dosage, cross-linking degree, and individual differences on metabolic pathways are minor and generally do not result in significant changes. Therefore, for products made from the aforementioned established materials, it is not necessary in principle to provide in vivo metabolic study data for the product. Existing literature can be provided as support, or the product's safety can be verified through biocompatibility evaluations. If a product uses a new absorbable material and lacks relevant research data on its metabolism in the body, an in vivo metabolism study for the product is required.
Under what circumstances can an application for a notification review of changes to the instructions for use be submitted?
According to Article 16 of the "Regulations on the Management of Instructions for Use and Labels of Medical Devices," changes to the content of the instructions for use that do not fall within the scope of registration changes should be notified in writing to the medical device registration approval department, along with the submission of relevant documents such as a comparison explanation of the changes to the instructions for use. After receiving an application for a notification review of changes to the instructions for use, CMDE will review the technical content of the application based on the requirements for file establishment. During the review process, if it is found that the application content involves issues that require the registrant to provide supporting documentation, a notice of acceptance for correction will be issued, specifying the specific problems with the application and the documentation that the registrant needs to submit. If, upon review, it is determined that the changes do not fall within the scope of the notification for changes to the instructions for use, the notice of acceptance for correction will clearly specify the non-conforming content and reasons, as well as the process for handling the changes through registration modification.
Is laboratory validation always necessary for the viral safety of animal-derived products?
The risk varies depending on the animal source, production process, and application scope of the products. For some common viral inactivation processes, such as organic substances, radiation, and strong acids, the procedures and methods are relatively mature and there is abundant reference literature available, making it unnecessary to perform laboratory validation for each one. For animal-derived products, especially those with well-established raw material applications, the effectiveness of viral inactivation can be evaluated using literature or historical data.
Do medical device products (non-in vitro diagnostic reagents) need to submit research data on stability or packaging validation for different batches of products?
For most medical devices (non-in vitro diagnostic reagents), the stability and shelf life generally depend on the raw materials used and aging mechanisms, such as thermal aging and photoaging. If the performance of raw materials, manufacturing processes, and packaging materials remains stable, different batches should not affect the product's stability and efficacy in principle. Therefore, whether it is necessary to submit research data on stability or packaging validation for different batches should be considered in conjunction with the product's characteristics and technical requirements. If the product has special properties, such as containing bioactive substances, submitting research data for different batches may be considered. In other cases, it is not mandatory in principle.
How should the temperature for real-time stability studies of passive medical devices be determined? What documentation should be submitted?
In theory, the temperature for real-time stability studies of products should generally be the same as the storage temperature. If there are specific regulations, these should be followed first, such as in GB/T 11417.8-2012 "Ophthalmic optics - Contact lenses - Part 8: Determination of shelf-life," which specifically sets the stability study temperature for corneal contact lens products at 25±2°C. For medical devices that are required to be stored at room temperature and have no special regulations, the temperature for real-time stability validation is not strictly enforced to be at 25°C±2°C. Documentation should be provided based on the characteristics of the product. For medical devices that require a specific storage temperature, validation studies should be conducted at that specified temperature.
For hip joint system products, if registering the liner separately, requirements for its matching outer cup must be specified. If there is no already registered matching outer cup, should it be registered together with the outer cup product?
When an applicant applies for the separate registration of a liner product, they need to provide relevant information about the outer cup intended for use with it, including materials, structural design, and model specifications, as well as related research and testing data on compatibility performance, such as press-out tests, rotational stability tests, and lever-out tests, along with relevant discussions. If there is no already registered matching outer cup, it can be declared together with the matching outer cup product or declared separately.
When registered medical devices (in vitro diagnostic reagents) are subject to changes in mandatory standards referenced in their technical requirements, there are scenarios where re-registration is not required.
The regulation specifies that if the registration certificate and its annexes for the already registered products remain unchanged and comply with the new mandatory standards, re-registration is unnecessary. This includes two cases: 1. The declared product has applicable mandatory standards. The technical requirements of the product cite the mandatory standards either by "directly quoting the specific content of the mandatory standard clauses," "standard number," or "standard number + year code." When the mandatory standard is updated, and the standard number and/or year code changes, but the content of the mandatory standard clauses cited in the product's technical requirements remains unchanged. 2. The declared product does not have applicable mandatory standards. The technical requirements of the product refer to the clauses of a certain mandatory standard. When the mandatory standard is updated, and the standard number and/or year code changes, the content of the mandatory standard clauses referred to in the product's technical requirements remains unchanged; or the content of the referred clauses changes, but the product's technical requirements still refer to the clauses of the previous version of the standard. In the above situations, if the product's technical requirements remain unchanged or only the referenced standard number and/or year code are updated, there is no need to undergo re-registration. This procedure also applies to the management of in vitro diagnostic reagents involving updates and replacements of national standards.
How to determine if the application for renewal registration is made six months before the expiration of the medical device registration certificate?
If the medical device registration certificate is nearing expiration and needs to be renewed, the registrant must apply for renewal registration six months before the expiration of the certificate and submit the required application materials accordingly. If the application materials are incomplete or do not meet the legal format, requiring correction, CMDE will indicate the registrant's initial application date for renewal registration in the acceptance notification for correction. When the registrant reapplies for renewal registration after making corrections, they must submit the acceptance notification for correction. CMDE will determine whether the application for renewal registration was made six months before the expiration of the medical device registration certificate based on the initial application date for renewal registration indicated in the acceptance notification for correction and will review the application materials in accordance with the regulations.
How should the inclusion and exclusion criteria for subjects be established in the clinical trial design of in vitro diagnostic reagents?
In the clinical trials of in vitro diagnostic reagents, inclusion and exclusion criteria for subjects should be reasonably set based on the intended use and applicable population of the product. It is crucial that the clinical trial subjects come from the population intended for the product's use, such as individuals with specific symptoms, signs, physiological or pathological states, or certain epidemiological backgrounds. Enrolling subjects outside the target population may introduce selection bias, leading to clinical trial results that do not reflect the true performance of the product. For example, in vitro diagnostic reagents intended for the auxiliary diagnosis of a particular disease should not randomly include a large number of asymptomatic healthy subjects in clinical trials. Clinical trials for hepatitis B, hepatitis C, HIV, and syphilis antibody testing reagents should not include a large number of preoperative screening patients who do not exhibit relevant symptoms or signs. Such inclusion criteria could lead to a deviation in the clinical specificity evaluation of the product from its true performance.