Due to the widespread interest from industry and because of substantial modifications introduced in several sections, it was agreed to engage with stakeholders a second targeted consultation on the updated draft guidance focusing on the sections and/or significantly modified paragraphs. In parallel, the document will also be submitted to PIC/S and WHO.

52 pages divided into 11 sections - the second draft has grown in volume by additional two pages. The new title Annex 1: Manufacture of Sterile Products (formerly Manufacture of Sterile Medicinal Products) clarifies the extended scope of application also for active substances, sterile excipients, primary packaging materials and finished dosage forms, packed sizes from single to multiple units, processes (from highly automated systems to manual processes) and technologies such as biotechnology, classical manufacturing of small molecules and closed systems.

The application of the principles of quality risk management (QRM) are further emphasized. QRM applies to this document in its entirety and is not dealt with in a single section only. In the case of specific information such as limit values, these should be regarded as minimum requirements. Microbial, particulate and pyrogen contamination in the finished product should be prevented this way. For this purpose, the use of appropriate technologies such as Restricted Access Barriers Systems (RABS), isolators, robotic systems, rapid microbial testing and monitoring systems are mentioned.

In the area of quality assurance, all critical control points must be defined and the effectiveness of all controls (design, procedures, technical and organisational measures) and monitoring measures must be evaluated.  The CCS (Contamination Control Strategy) should be continuously updated with the aim of continuously improving the manufacturing and control methods over the entire life cycle of the product. Non-conformities should be comprehensively analysed.

We will shortly compile more detailed information on the second draft of Appendix 1 which will be published in our weekly newsletter LOGFILE.

Source:

EC: Medicinal Products

EC: Annex 1: Manufacture of Sterile Products