Protective Airflow including ‘First Air’ in GMP Aseptic manufacturing

Abstract

Good Manufacturing Practices (GMP) related to sterile product aseptic manufacturing environments rely on protective airflow mechanisms to ensure the control over airborne contamination. Alongside the protective airflow, pressure differentials that drive airflow cascade ensure GMP compliant contamination control of airborne contamination that may include Microbial carrying particles (MCPs). Airflow visualisation qualification by smoke studies has been clarified as a GMP requirement in EU & PICS Annex 1. The scope of Annex 1 applies to manufacture of sterile medicinal products together with bioburden control processes where bioburden in intermediates, substances, APIs and non-sterile products can also impact patient safety so a wide scope of protective airflow applications is applied. As a GMP requirement (included in 2008 version of Annex 1): It should be demonstrated that air-flow patterns do not present a contamination risk, e.g. care should be taken to ensure that air flows do not distribute particles from a particle generating person, operation or machine to a zone of higher product risk.' Within Annex 1: 2023, the concept of First Air has emerged as a critical element. First Air is defined as “filtered air that has not been interrupted prior to contacting exposed product and product contact surfaces with the potential to add contamination to the air prior to reaching the critical zone.” The requirement for extensive smoke studies and the integration of First Air protection as a mandated aspect in GMP regulations has brought to the fore an imperative need for a deeper comprehension of airflow dynamics and their implications on sterile product Aseptic manufacturing. This shift beckons us to explore the nuances of protective airflow, particularly in the context of Computational Fluid Dynamics (CFD) analyses, to discern the efficacy of airflow patterns in different scenarios. Stakeholders involved in Annex 1 implementation have been impacted by introduction of the First Air protection requirement, considering design and in qualification via smoke study airflow visualisation. Such requirements must follow QRM principles where process understanding and knowledge of contamination hazards are essential to mitigate risks in compromise of product quality and potential harm to patients. Risk mitigations must take a Quality by Design (QbD) approach as monitoring alone does not provide assurance of product sterility or in meeting defined bioburden limits.