Preamble

The purpose of this guideline is to guide the registration applicant to prepare and write the registration information of the monkeypox virus nucleic acid test reagent, and also to provide reference for the technical review department.

This guideline is a general requirement for monkeypox virus nucleic acid test reagents, the applicant should determine whether the content is applicable according to the specific characteristics of the product. If it is not applicable, the applicant should specify the reasons and the corresponding scientific basis, and enrich and refine the content of the registration declaration according to the specific characteristics of the product.

This guideline is for registration applicants and technical reviewers to use the guiding documents, but does not include the administrative matters involved in the review and approval, and not as a mandatory implementation of regulations, should be used under the premise of complying with the relevant laws and regulations of this guideline. If there are other methods that can meet the requirements of the relevant regulations, they can also be used, but need to provide detailed research information and validation information.

Scope of application

This guideline applies to reagents for the in vitro qualitative detection of monkeypox virus nucleic acid in samples of skin lesions (including swabs of rash surfaces and/or exudates; pox blisters; samples of pox scabs or pox blisters of skin and mucous membranes, etc.), pharyngeal swabs, and blood, etc., by using the real-time fluorescence PCR method.

For monkeypox virus nucleic acid detection reagents using other methodologies, some of the requirements may not be fully applicable or the content described herein may not be comprehensive enough, and the applicant should refer to this guideline to evaluate the applicable part according to the product characteristics and supplement other evaluation information.

This guideline applies to the application for registration of monkeypox virus nucleic acid test reagent and the change of registration application. This guideline is written for the monkeypox virus nucleic acid test reagent registration information, other matters should be in line with the "on the announcement of in vitro diagnostic reagent registration information requirements and approval of the document format of the announcement" and other related regulations, and recommended to refer to the "qualitative test reagent analytical performance evaluation of the registration of the review of the Guiding Principles," and other applicable technical documentation requirements.

Key points for registration review

Regulatory information

1. Product name and classification code

The product name should be in line with the "Administrative Measures for Registration and Filing of In Vitro Diagnostic Reagents" and relevant regulations, such as Monkeypox Virus Nucleic Acid Detection Kit (Fluorescent PCR Method). According to the Rules for Classification of In Vitro Diagnostic Reagents, the product is managed according to the third category of in vitro diagnostic reagents, and the classification code is 6840.

2. Other information also includes the list of products, related documents, records of contact and communication with regulatory authorities before filing, and documents such as declaration of conformity.

Overview information

Synthesis information mainly includes an overview, product description, intended use, declaring the history of the product listing and other content to be explained. Detailed description of the technical principles and detection processes used in the product. Provide the detection throughput of different applicable models, i.e. the maximum number of samples that can be detected in one test. Provide the time for nucleic acid extraction (manual and automatic extraction methods should be specified separately) and PCR amplification, as well as the time required for the whole detection process. Provide the assay time for the minimum and maximum number of samples to be tested for different assay processes. Comparison with similar products already on the market, including sample type, detection principle, detection of target genes, components, internal standards, controls, reading rules, analytical performance and clinical performance.

The intended use specifies the target genes to be detected by the product, and genes with relatively high conservativeness and specificity should be selected, and the amplification efficiency of the genes should also be taken into consideration. Relevant guidelines or literature should be provided for the selection of detection genes, and the sensitivity and specificity of the detected genes should be analyzed to see if they meet the clinical needs.

Non-clinical information

1. Analytical performance study

The applicant for registration shall use the kits produced in an environment that complies with the quality management system to conduct all analytical performance studies, and submit specific test protocols, test data, statistical analysis and other detailed information.

The basic information of the samples used in the analytical performance evaluation should be clearly defined, such as the source of samples, sample type, collection and processing methods, dilution methods, the process of value setting and data, etc. For monkeypox virus positive samples used in the study, scientific and reasonable methods should be used to determine their negativity and concentration levels, and specific test information should be submitted. Samples used for analytical performance assessment should generally be real samples, including clinical samples and viral cultures, and samples from within or outside the country may be used for the study. If post-dilution testing is involved, a negative matrix consistent with the applicable sample type should be used. Plasmids, etc. may not be used for analytical performance assessment. Samples used in precision, detection limit and inclusivity studies should be independent of each other.

2. Stability studies

The stability of the declared reagents mainly includes real-time stability (expiration date), open stability, transportation stability, airborne stability (if applicable) and freeze-thaw limit, etc. The applicant can choose a reasonable stability study program according to the actual needs. Stability study information should include specific implementation programs, detailed study data and statistical analysis of conclusions. For real-time stability studies, should provide at least three batches of products in the actual storage conditions until the finished product after the expiration date of the study information. For the open bottle stability study should simulate the real use of the situation, including the open bottle stability of the bottle frequency and open time.

3. Positive judgment value study

Positive judgment value is generally declared for the product test virus nucleic acid positive Ct value. Positive judgment value of the study with the sample source should have diversity and representativeness, taking into account different time, geography, different stages of infection and physiological status and other factors, as far as possible to incorporate more weakly positive samples, negative samples should contain easy cross-pathogens with high concentrations of samples. When conditions permit, it is recommended to cover the current prevalent strains for positive judgment value studies. If there are gray areas in the judgment value, confirmation information of the gray areas should be provided.

If the product is applicable to different sample types, validation of the positive judgment value for each sample type is required.

Submit a list of background information for the samples used in the positive judgment value study, including at least gender, age, clinical diagnostic information, sample source organization, and test results.

Provide information on the methods and studies used to determine the range of internal standard test results.

4. Other information

Clinical evaluation information

The conduct of clinical trials, the formulation of protocols and the writing of reports shall comply with the requirements of relevant regulations and the Technical Guidelines for Clinical Trials of In Vitro Diagnostic Reagents, and if there are updates to the relevant regulations and documents, the clinical trials shall comply with the updated requirements.