Cell & Gene Covers the “Challenges with Implementing Annex 1 at the Global Level” Session from the 2026 ISPE Aseptic Conference
During the 2026 ISPE Aseptic Conference, Franck Bure, Principal Quality Technical Manager, Genentech/Roche presented “Challenges with Implementing Annex 1 at the Global Level.” Bure spoke with Cell & Gene ahead of the session to provide insights on how organizations can close capability gaps and move toward a unified global governance model.
Bure explores how the global biopharmaceutical industry continues to struggle with the practical and regulatory implications of the revised EU GMP Annex 1 for sterile manufacturing. Although companies rushed to implement the updated requirements in 2023, the initial sense of accomplishment has given way to a more sobering reality: regulators are now scrutinizing not just whether companies claim compliance, but whether they can demonstrate it with data, consistency, and a defensible contamination control strategy.
A central theme of the article is the shift from risk assessment-based justification to evidence-based compliance. Historically, companies could defend decisions such as hold times, personnel limits, or the use or omission of pre-use post sterilization integrity testing (PUPSIT) through risk assessments. Regulators are no longer accepting this approach. Instead, they expect manufacturers to provide objective data—such as airflow visualization studies, environmental monitoring (EM) results, and aseptic process simulation (APS) outcomes—to prove that their processes consistently meet sterility assurance expectations. This shift has been jarring for companies that believed they were compliant, only to receive unexpected findings from agencies like the US Food and Drug Administration and Swissmedic. Bure explains that this is not a failure of industry effort but a reflection of how rapidly regulatory expectations have evolved.
The article also highlights the ambiguity of Annex 1, which some might interpret as a regulatory flaw. Bure argues the opposite: the ambiguity is intentional, designed to place accountability on manufacturers rather than provide prescriptive checklists. Annex 1 defines the “what,” but leaves the “how” to industry, requiring companies to deeply understand their processes and justify their controls scientifically. However, this flexibility has led to inconsistent interpretations across global sites and inspectorates. For example, agencies differ in how they interpret personnel flow requirements, APS bracketing, and EM qualification expectations. These inconsistencies have created what Bure calls a “calibration phase,” where both regulators and manufacturers are still aligning on the practical meaning of the updated guidance.
Technical capability gaps further complicate compliance. Some older fill lines simply cannot meet modern airflow and first-air protection expectations, while even newer lines may require redesigns if components obstruct critical zones. At the same time, many organizations lack the internal expertise needed to interpret Annex 1’s more complex, data driven requirements. Bure describes how Roche addressed this by implementing a global governance model, with centralized process owners and technical experts ensuring that all sites—regardless of geography—apply the same standards, methods, and interpretations. This approach reduces variability and ensures that every site can withstand regulatory scrutiny.
The article also delves into two of Annex 1’s most contentious topics: restricted access barrier systems (RABS) versus isolators and PUPSIT. Regulators increasingly favor isolators because they provide continuous isolation and reduce human interaction, and they are scrutinizing RABS systems more aggressively, especially when airflow visualization reveals first-air obstructions. In some cases, regulators have required companies to develop exit strategies for legacy lines that cannot meet expectations. Meanwhile, the long debated PUPSIT requirement has effectively become nonnegotiable. Regulators now consider it mandatory unless physically impossible—a threshold that is rarely met. As a result, companies have shifted from debating the requirement to optimizing its execution, typically performing PUPSIT under Grade A airflow to mitigate contamination risk.
Since Annex 1 has become a global benchmark, not merely a European regulation, agencies worldwide are now aligning with its principles. Bure emphasizes that achieving this requires standardized equipment, procedures, and governance structures across all sites, ensuring that sterile manufacturing meets the same high standard everywhere. The 2026 ISPE Aseptic Conference served as a platform for these insights and more, providing life sciences professionals with real world knowledge, and the opportunity to learn from their fellow industry members.
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