Editorial | Open Access | Published 26th March 2026

GUEST EDITORIAL: Putting Airborne contamination control into focus.

Author: James Drinkwater

Alongside surface contamination control airborne contamination control has long been a requirement in GMP manufacturing. The PHSS has taken the initiative to complete some scientific research to improve knowledge around the attributes and characteristics of protective airflows, including ‘First Air’ as defined in EU GMP & PICS Annex 1.

The term ‘First Air’ introduced into the revised Annex 1 is starting to be impactful on airflow management within barrier technologies where uni-directional protective airflow (UDAF) passes over complex processing equipment during aseptic manufacturing, particularly filling of sterile medicinal and advanced therapeutic products. It is not just the management and visualisation of protective airflows that have come into focus but also consideration is given to the complex geometrics and airflow interactions that are impacted by aerodynamic design and process intervention operations, via barrier gloved hands and/or robotic arms.

Airflow visualisation is now under more scrutiny as a key requirement of protective airflow qualification in Annex 1, via smoke studies. But to better understand what protective airflow, including ‘First Air’ should look and perform like, more characterisation is required. Inevitably there will be turbulences within UDAF protective airflows as air interacts with complex processing equipment. Airflows will speed up or slow down when passing over processing equipment and hence deviate from the expected (guidance level) 0.45m/s +/- 20% airflow velocity. To reduce subjectivity as to whether the qualification study outcomes were acceptable or not, airflow pattern characterisation is required so expectations on performance can be translated into acceptance criteria.

The PHSS is in the process of not only characterizing protective airflows, including First Air but also setting ‘Rules for Compliance’ that can apply both in design and airflow visualisation qualification stages for GMP compliance to Annex 1. The combination of CFD studies, applied at design phases (and potentially DQ: design qualification) are complementary to the formal smoke study OQ: operational qualification where fully dynamic studies apply at-rest and in-operation through set-up and operational process steps, including intervention studies.

The PHSS Cleanroom Airflow definition guidance is scheduled for update early 2026 to include Protective Airflows and First Air alongside the current definitions of UDAF, Localised UDAF and Grade A Air supply (AAS). This airflow definition guidance will be an important reference to regulators and industry alike.

The first stage of the PHSS airflow visualisation research study was published in the EJPPS December 2025 issue with subsequent training on the outcomes of the research completed for regulatory authorities including USA FDA, with 100 attendees from CBER. A more in-depth two half-days online PHSS airflow visualisation training is upcoming for access to all stakeholders: GMP inspectors, GMP auditors, pharma industry, technology manufacturers and those involved in protective airflow qualification studies.

By increasing knowledge, through research, there is an opportunity to make improvements on current equipment and process designs that operate in UDAF airflows within barrier technology but also reduce subjectivity in classical airflow visualisation smoke studies. It will also permit a better understanding of what attributes and characteristics protective airflows, including First Air, should have and what acceptable criteria can be applied in qualification studies having more clarity set against published references.

Training Teaser: Images from CFD studies considering protective airflow patterns and velocity vectors over open sterile product containers before filling and at the point of fill. What do they tell us about First Air protection? Note the yellow/ green vectors are at expected velocities and blue are near 0 m/s (dead air).

• Is the First air that exits the UDAF supply HEPA filter supposed to be the first air that reaches and protects critical process points? As this is unlikely to be possible with air passing over other surfaces e.g. air diffuser screens. velocity probes, filling needle holders, then what ‘Rules’ need to be applied for First Air to meet the requirements of being protective without addition and compromise on route of particulate or potentially microbial contamination.

• Is there protective airflow inside a product container over the product if the container acts as a dead-leg? If so, how do we characterise this as First Air protection

• What is the impact of the filling needle holder and its design on First Air?

• When product enters the container of dead-leg air does displacement mean product aerosols release outside the container and if so, how far? Important for filling any toxic or hazardous product.

• What is the comparison between protective airflow applied vertically as down flow or horizontal flow when considering First Air protection?

• What does First Air protection look like if there is a wider area to protect than a single product container e.g. product containers in nests, groups of containers on a rotary indexing table, feeder hopper and bowl?

• What happens if the protective airflow is disrupted by barrier technology gloves or robotic arm movement?

All questions will be answered and discussed in the training