Development process of in vitro diagnostic(IVD) reagents



1. What is the R&D process of in vitro diagnostic reagents?
In recent years, the in vitro diagnosis market has developed rapidly, especially since 2019, the in vitro diagnosis industry has developed rapidly due to the impact of nucleic acid detection of the new coronavirus pneumonia. In vitro diagnostic kits are the main products of in vitro diagnostics. The development of an in vitro diagnostic reagent mainly includes the following links:

1. Project preparation stage
Including project research, project evaluation, design input, etc. First of all, it is necessary to determine the direction of the project, including the target to be tested, the intended use, and the application scenario. The second is to clarify the market capacity and application prospects, including the incidence of corresponding diseases, and whether there are similar products in the market, that is, analysis of competing products. As well as clarifying the market evaluation of similar products and the associated clinical diagnosis or laboratory testing methods, etc. After determining the direction, it is necessary to consult a large number of literature and industry reports to fully understand the progress and application of target research, confirm the feasibility of detection methods and technologies, and confirm the environmental conditions of equipment, functions and composition of project developers, etc.

After the project approval review, the product design input is carried out. In the design input, we must consider all aspects as much as possible, determine the performance parameters and standards of the product, clarify the intended use, etc., so as to avoid finding many deficiencies in the output. The information at this stage will be aggregated into a document for product registration and declaration, that is, “Product Summary Information”.

2. Product development stage
After the completion of the project, the development phase of in vitro diagnostic reagents can be started. The early stage of development includes the screening of raw materials, the research of main production process and reaction system, and the research stage of product verification:

(1) When screening raw materials, at least three or more are screened to ensure that the final selected supplier has a complete quality system, and the raw materials can provide qualified quality standards, factory inspection reports and other materials.

(2) Determine the amount of reagents, the ratio of various raw material formulations, reaction conditions, working temperature and other parameters in the production process and reaction system research stage. According to the research and development data of raw material screening, production process and reaction system research, output corresponding documents, and carry out kit production in GMP workshop. This stage is the most important stage, and it is also the stage where the project schedule is most often deviated.

(3) In the verification research stage, the three batches of kits produced in the GMP workshop are used for product verification research, including product analysis performance evaluation, product stability research, determination of positive judgment value or reference interval and other related work.

3. Registration inspection stage
After the above stages are completed, the registration inspection stage can be entered. Three batches of kits continuously produced in the GMP workshop are used to apply for registration inspection sampling, and then the registration inspection verification is carried out. The data at this stage will be aggregated into the document when the product is registered and declared, that is, the “Registration Test Report”.

4. Clinical trial stage
After obtaining the registration test report, the clinical trial phase can be started. The clinical trial stage includes pre-clinical preparation, formulation of clinical trial plan, signing of ethical clinical agreement, clinical trial filing, clinical trial implementation, clinical trial summary, etc. The data at this stage will be aggregated into the documents for product registration application, namely “Clinical Trial Protocol” and “Clinical Trial Report”.

5. Registration review stage
The registration review stage entered after the clinical trial is completed is that the Drug Administration conducts a systematic evaluation of the safety and efficacy studies and results of the IVD reagents to be marketed according to the application of the registration applicant and in accordance with the corresponding legal procedures, to decide whether to agree with the process of their application. This stage includes writing and submitting IVD registration application materials, system assessment, corresponding supplementary work according to the supplementary notice, and submission of supplementary materials. After all the above audits are passed, the certificate can be obtained. The data at this stage will be aggregated into documents required for product registration, such as the “Quality System Assessment Report”. After the registration review is passed, the certificate can be obtained, and the registration of the kit development is successful.

2. What are the difficulties in the development of in vitro diagnostic kits
The development of in vitro diagnostic kits is not that simple. There are many difficulties in the development process, including:

1. First, find some patients with the same disease, and then start to find disease-specific signals through basic scientific research. These signals can distinguish patients from normal people in terms of quality or quantity, and can also be distinguished from other similar diseases. Open, this is the initial difficulty of research and development.
2. It is not enough to find this signal that can be used for diagnosis. It is also necessary to develop a method that can repeatedly qualitatively and quantitatively identify this signal. The method is best to make the material easy to obtain, accurate in detection, fast, light and cheap, which is the difficulty in the research and development process.
3. After the research and development is completed, it needs to enter the market. It needs production, clinical verification, approval, doctor and patient education, market promotion, etc.