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EDQM Guidance: Content of the Dossier for Sterile Substances

The European Directorate for the Quality of Medicines & HealthCare (EDQM) has released a draft guideline titled "Content of the Dossier for Sterile Substances" for public consultation. This guideline outlines the specific requirements for the documentation and data necessary to demonstrate the quality, safety, and efficacy of sterile substances. It aims to standardize the submission process for obtaining Certificates of Suitability (CEP) for sterile substances, ensuring that they meet stringent regulatory standards.

This document serves as a guide for applicants seeking to obtain a Certificate of Suitability (CEP) for a sterile substance. It outlines the necessary documentation and requirements for such applications, emphasizing the importance of compliance with relevant guidelines and regulations.

The acceptability of CEP applications for sterile active substances applies to manufacturing processes where sterilization operations required to obtain the sterile material are performed either at the active substance manufacturing site or at a different site. The CEP holder is responsible for the manufacturing steps to obtain the active substance and its sterilization, and full documentation should be provided in the CEP application.

Documentation to be provided for the Sterile Substance

Applicants are expected to provide relevant information about the sterile aspects of the manufacturing process in section 3.2.S.2.5. This includes justification for the method of sterilization, details of manufacturing areas, summary of manufacturing process related to sterile filtration/aseptic processing, information on filters used, validation of filters used, sterilization of filters and processing equipment, pre-filtration bioburden, re-use of filters, aseptic processing, process simulation/validation, sterilization of packaging, and re-test period.

Justification for Method of Sterilization

The document highlights that the sterile substance is generally manufactured by sterile filtration. Other methods such as dry heat sterilization, ionizing radiation, or ethylene oxide gas can also be used, but must be adequately justified. Details of the sterilization process, including filtration conditions and parameters, should be included in the dossier.

Manufacturing Areas

The manufacture of sterile substances should be carried out in appropriate cleanrooms. The use of equipment such as RABS, isolators, or other systems should be considered to minimize the risk of contamination. Manufacturing area grades for each production step leading to the packaged sterile substance should comply with relevant guidelines.

Summary of Manufacturing Process

Adequate narrative and schematic description of the steps leading to the sterile active substance in its final container is expected. Details such as solvents, temperature, equipment, and filtration should be included. The manufacturing batch size and information on filters used should also be stated.

Obtaining a Certificate of Suitability (CEP) for a sterile substance requires meticulous attention to detail and compliance with relevant guidelines and regulations. By providing comprehensive documentation and justification for the sterilization process, applicants can enhance their chances of a successful application.

For more details, you can visit the full guidance document here. The draft document is now available for public consultation in the consultation space. The consultation deadline for this document is 15 August 2024. After the consultation phase, the final guideline will be made available on the EDQM website.


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