Our CEO Jari Suhonen express valuable insights about Annex 1 which was set to become effective from 25 August 2023, except for point 8.123 which is postponed until 25 August 2024.
This annex is an integral part of the EudraLex Volume 4, which encompasses the Good Manufacturing Practice (GMP) Guidelines and interpreted as law by the European Commission. Notably, it underwent revisions and expansions in 2020 and 2021, with a key emphasis on focusing risk management and contamination control strategies.
Jari Suhonen, CEO of Feicon Oy, emphasizes, “Cleanroom compliance is not just about meeting regulations; it’s about safeguarding users who rely on these critical products.”
Unveiling Changes in EU GMP Annex 1 Regarding Cleanroom and Clean Air Equipment Qualification
Why EU GMP Annex 1 Matters?
The revised Annex 1 mandates that cleanrooms and associated equipment, including unidirectional airflow units (UDAFs), Restricted Access Barrier Systems (RABS), and isolators, must undergo a comprehensive qualification process aligned with stipulated environmental standards. Qualification involves rigorous assessment to ensure compliance with intended use and required cleanliness levels. The qualification process encompasses both “at rest” and “operational” states, with the objective of validating and sustaining appropriate environmental conditions.
The Cleanroom Qualification Checklist
The methodology for cleanroom and equipment qualification adheres to the guidelines outlined in Annex 15, and it is essential to differentiate cleanroom qualification from operational environmental monitoring. The qualification process encompasses a range of assessments, including:
- Installed Filter System Testing: Verification of filter system leakage and integrity.
- Airflow Testing: Measurement of volume, velocity, and direction of airflow.
- Air pressure Difference Testing: Evaluation of air pressure differentials.
- Microbial airborne and surface contamination: Assessment of airborne and surface microbial
presence. - Temperature and Relative Humidity Tests: Measurement of temperature and humidity levels.
- Recovery and Containment Tests: Evaluation of system recovery and containment integrity.
The Dynamics of “At Rest” and “In Operation”
Cleanroom classification integral to the qualification process, employs measurements of particle concentration at various particle sizes (≥ 0.5 and 5 µm) during both “at rest” and “in operation” states. The classification aligns with the ISO 14644 standards, determining particle limits that should be maintained within each cleanroom grade. Cleanroom classification activities should be strategically planned to prevent any disruption to process or product quality.
To ensure unidirectional airflow efficacy, the speed of air supplied by such systems is determined based qualification protocol and aligns with defined velocity ranges (0.36 – 0.54 m/s). Microbial contamination assessments, guided by risk assessments and process understanding, inform the qualification process, with sampling locations and limits changes to each cleanroom grade (A, B, C, and D).
Adapting to Changes with Confidence:
Cleanrooms evolve over time. EU GMP Annex 1 mandates thorough assessments after any changes, such as alterations in cleanroom design or equipment. Requalification of cleanrooms and clean air equipment is mandated at defined intervals, encompassing assessments such as cleanroom classification, filter integrity, airflow volume, air pressure, and, where applicable, velocity testing. The frequency of requalification varies based on cleanroom grade, with shorter intervals for higher grade cleanrooms (A and B) compared to lower-grade (C and D) areas which is 6 months and 12 months respectively. Requalification is also necessitated after remedial actions or significant changes to equipment, facility, or processes.
In the words of Jari Suhonen, “At Feicon Oy, we’re committed to upholding the highest standards in cleanroom practices. Our expert services cover cleanrooms, validation, and quality development, aligning your operations with the latest EU GMP Annex 1 guidelines.”
Let’s work together to uphold the highest standards of cleanroom operations and product quality in this ever-evolving pharmaceutical landscape.