Drugdu.com expert's response:

In the case of in vitro diagnostic reagents, if changes occur to matters not specified in the registration certificate and its attachments, there is no need to apply for a variation of registration. According to the "Measures for the Registration and Filing of In Vitro Diagnostic Reagents" and relevant regulations, when changes occur to matters not specified in the registration certificate and its attachments for in vitro diagnostic reagents, enterprises are not required to apply for a variation of registration with the original registration authority. However, they must control the changed content through their internal quality management systems, with the specific requirements as follows:

I. Scope of Changes Not Involving the Registration Certificate

Changes to matters not specified in the registration certificate and its attachments typically include, but are not limited to:

Adjustments to packaging formats or specifications (e.g., changing from bulk packaging to single-dose packaging);

Changes in reaction formats (e.g., changing from a colloidal gold test card format to a cup format);

Textual modifications to the product instructions (e.g., explanations of labels, formatting optimizations, etc.);

Other technical detail adjustments that do not affect the safety and effectiveness of the product.

II. Core Obligations of Enterprises

Risk Analysis

Enterprises need to conduct a comprehensive risk assessment of the changed content, identify potential risk points (e.g., increased evaporation loss and shortened shelf life due to packaging changes), and develop targeted control measures.

Verification and Confirmation

Packaging changes: Analytical performance studies on the changed packaging specifications must be conducted to verify whether its stability and in-use stability meet the requirements.

Instruction modifications: If changes involve textual content such as label explanations, it must be ensured that they comply with the YY/T 0466 series standards or ISO 15223 standard, and the modifications should be explained during the renewal of registration.

Other changes: Depending on the type of change, performance tests, stability studies, etc., may need to be carried out to ensure that the change does not affect the safety and effectiveness of the product.

Quality Management System Control

Enterprises need to incorporate change control procedures into their quality management systems, clearly defining processes for the identification, review, verification, confirmation (where appropriate), and approval before implementation of changes, and forming documented records. If changes involve multiple aspects (e.g., multiple changes occur simultaneously), a comprehensive assessment of their overall impact on the safety and effectiveness of the product is required.

III. Differentiation from Changes Involving the Registration Certificate

If changes involve content specified in the registration certificate and its attachments (e.g., product name, packaging specifications, main components, intended use, product technical requirements, product instructions, production address of imported in vitro diagnostic reagents, etc.), an application for a variation of registration or filing must be submitted to the original registration authority. For example:

Change of main raw material supplier: If the supplier information is specified in the registration certificate attachments, an application for a variation of registration is required; if not, the enterprise controls the risks on its own.

Major adjustments to production processes: If they affect the safety and effectiveness of the product, an application for a variation of registration is required; if they are minor optimizations, they are controlled through the quality management system.

IV. Regulatory Requirements and Compliance Recommendations

Regulatory Basis

Enterprises need to comply with Article 78 of the "Measures for the Registration and Filing of In Vitro Diagnostic Reagents" (Order No. 48 of the State Administration for Market Regulation) and relevant documents such as the "Guidelines for the Review of Variation Registration of In Vitro Diagnostic Reagents."

Compliance Recommendations

Establish a change management ledger to record all change matters and their handling results.

Conduct regular internal audits of the change control procedures to ensure their effectiveness.

Stay informed of regulatory updates and promptly adjust change management strategies to comply with the latest requirements.