Abstract
A practical, risk-based monitoring approach using the combined data collected from actual experiments and computer simulations was developed for the qualification of an EU GMP Annex 1 Grade B, ISO Class 7 area. This approach can locate and minimize the representative number of sampling points used for microbial contamination risk assessment. We conducted a case study on an aseptic clean room, newly constructed and specifically designed for the use of a restricted access barrier system (RABS). Hotspots were located using three-dimensional airflow analysis based on a previously published empirical measurement method, the three-dimensional airflow analysis. Local mean age of air (LMAA) values were calculated based on computer simulations. Comparable results were found using actual measurements and simulations, demonstrating the potential usefulness of such tools in estimating contamination risks based on the airflow characteristics of a clean room. Intensive microbial monitoring and particle monitoring at the Grade B environmental qualification stage, as well as three-dimensional airflow analysis, were also conducted to reveal contamination hotspots. We found representative hotspots were located at perforated panels covering the air exhausts where the major piston airflows collect in the Grade B room, as well as at any locations within the room that were identified as having stagnant air. However, we also found that the floor surface air around the exit airway of the RABS EU GMP Annex 1 Grade A, ISO Class 5 area was always remarkably clean, possibly due to the immediate sweep of the piston airflow, which prevents dispersed human microbes from falling in a Stokes-type manner on settling plates placed on the floor around the Grade A exit airway. In addition, this airflow is expected to be clean with a significantly low LMAA.
Based on these observed results, we propose a simplified daily monitoring program to monitor microbial contamination in Grade B environments. To locate hotspots we propose using a combination of computer simulation, actual airflow measurements, and intensive environmental monitoring at the qualification stage. Thereafter, instead of particle or microbial air monitoring, we recommend the use of microbial surface monitoring at the main air exhaust. These measures would be sufficient to assure the efficiency of the monitoring program, as well as to minimize the number of surface sampling points used in environments surrounding a RABS.
- Aseptic processing
- Environment monitoring
- Airborne microbial monitoring
- Three-dimensional airflow
- Local mean age of air
- Surface monitoring
- Risk assessment
Footnotes
- Copyright © Parenteral Drug Association. All rights reserved.
PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.
If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing.
Full issue PDFs are for PDA members only.
Note to pda.org users
The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.