Table of Contents
Table of Contents
Introduction
Scope
Group 1: Strategic Approach for Maximizing Use of CCS in GMP Facilities
Group 2: Equipment and Facilities
Group 3: Personnel Training and Procedures
Group 4: Applicability of EU Annex 1 to Low Bioburden Biologic Drug Substance Manufacturing
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Introduction
The pharmaceutical industry is encountering an increase in regulatory scrutiny related to sterile manufacturing, this is in part due to the update to Eudralex and PIC/S issuance of the updated Annex 1 for the manufacture of sterile medicinal products partly due to events such as the Pseudomonas aeruginosa contamination of eye drops of 2023. Inspection observations highlight gaps in alignment with the current state of manufacturing science, particularly in aseptic processing and contamination prevention. These gaps often stem from legacy equipment and facility designs, inadequate or misapplied risk assessments, and incomplete execution or documentation of process validation and monitoring that does not align with expectations described in Eudralex and PIC/S GMP Annex 1 (2022) or the Code of Federal regulations, such as 21 CFR 210 and 211 as interpreted in the USFDA Guidance for Industry – sterile drug products produced by aseptic processing (September 2004). Despite the identified challenges, industry remains committed to supplying patients with high-quality medicines that meet evolving standards and best practices, even as expectations evolve with the progression of technology and scientific understanding.
To safeguard patient supply while strengthening compliance, a practical, risk-based path is needed — one that recognizes changing expectations and provides actionable principles to mitigate risk during transitions to new equipment, facilities, and controls. This white paper responds to that need by consolidating contemporary expectations across contamination control strategy, aseptic process validation, equipment and facility design, and personnel practices. These propose a harmonized approach across industry which will ensure consistency during the development of aseptic processes and regulatory oversight. It explains how risk management supports sterility assurance and supply continuity, emphasizing that monitoring and aseptic process simulations should guide evaluations of control measures and inform future strategies, rather than justify inadequate designs or practices.
The white paper is intended to bridge near-term operational realities with longer-term investments in robust sterile and contamination-controlled operations. It outlines how manufacturers can prioritize control and monitoring of critical activities while adopting facility and equipment strategies aligned with current expectations. It also reinforces the essential role of qualified personnel, proper gowning, and disciplined behaviors in maintaining controlled environments and preventing contamination.
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Acknowledgements
The Global Pharmaceutical Manufacturing Leadership Forum exists to provide a neutral setting in which senior pharmaceutical industry thought leaders can engage in dialogue around critical industry issues with the objective to progress those areas of common interest to membership into tangible action. The Global Pharmaceutical Manufacturing Leadership Forum meets twice annually for one day. Meetings usually take place at the ISPE Europe Annual Conference in the spring and at the ISPE Annual Meeting & Expo in the fall. Ad hoc meetings are held throughout the year by the core team and various task teams for planning purposes and to progress the Global Pharmaceutical Manufacturing Leadership Forum agenda. Learn More
