The revised version of the EDQM guideline “Content of the dossier for chemical purity and microbiological quality of substances for pharmaceutical use” is now available and will be implemented as of 1st May 2024. This guideline and other key documents (QOS, top ten deficiencies), as well as the use of EMA SPOR/OMS ORG_ID and LOC_ID are essential to avoid a CEP dossier being blocked at receipt or receiving requests for additional information.
Changes introduced in this revised guideline aimed to align requirements with the current regulatory environment (since the previous version of this document was implemented in January 2019). In particular, the guideline has been updated with regards to certain information to be included in the 3 modules of the submission as described below.
In Module 1, particular attention should be paid to use the appropriate EMA SPOR/OMS ORG_ID and LOC_ID for the CEP holder and manufacturing sites, and the declarations given in annex of the application form should be duly filled in.
The Module 2 is the Quality Overall Summary (QOS) for which an updated template is now available. It serves as a concise overview of Module 3, highlighting the control strategy applied and how regulatory requirements are met to ensure the quality of the substance, and providing assessors with a clear understanding of the substance’s specification and manufacturing process. The QOS is a mandatory component of the CEP application and should be treated with utmost importance and consistency with Module 3. A poorly crafted or incomplete QOS can hinder the assessment process and lead to delays, potentially jeopardising the overall timelines to obtain a CEP.
The updates concerning the Module 3 include for example new requirements for CEP 2.0, encouragement to apply for a re-test period with possibility to refer to all ICH climatic zones and introduction of Post-Approval Change Management Protocol(s).
Other notable changes include amongst others, detailed expectations for sections related to the manufacturing process, starting materials and intermediates facilitating the understanding of the control strategy proposed. The need to build a comprehensive risk assessment based on ICH M7 and taking also into account the potential risk for formation and carry-over of nitrosamines has been added. Changes regarding submission of applications for sterile active substance are mentioned but will be covered by specific EDQM guidance.
The EDQM document “Top ten deficiencies in New Applications for Certificates of Suitability for chemical purity” helps also applicants to avoid deficiencies by giving expanded details on specific points of Module 3.
To enable an efficient treatment of CEP applications the EDQM will implement a stricter validation of applications at receipt and check whether the submission is in line with the requirements described in the revised guideline and the revised QOS template. The EDQM may therefore block applications at receipt from May 2024 in case these are considered deficient to start the assessment process.
Therefore applicants are strongly encouraged to use the revised guideline and the associated key documents for the preparation of the CEP applications they intend to submit: