Wednesday, January 24, 2024

How to do environment monitoring of microbial load in Class D area in Solid oral dosage form in pharma manufacturing facility

·         Class D areas are considered controlled support areas with relatively lower cleanliness requirements compared to aseptic processing zones (Grade A/B/C). While they may not directly handle sterile materials, they can still impact the overall cleanliness of the manufacturing process.

·         Microbiological monitoring focuses on detecting and quantifying airborne microorganisms. Ideally, this should be done at rest, meaning when the area is unoccupied and equipment is inactive. This provides a baseline assessment of the inherent microbial contamination level of the environment itself.

·         During operation, activities like granulation and mixing generate significant air disturbances, leading to increased particulate counts. These particles can act as carriers for microorganisms, potentially elevating the microbial count in the working condition. So, solely relying on operational monitoring might not accurately reflect the true microbial state of the environment.

Therefore, conducting both at-rest and operational microbiological monitoring provides a more comprehensive picture:

·         At-rest monitoring: Identifies potential contamination sources within the environment itself, independent of process activities.

·         Operational monitoring: Assesses the combined impact of the environment and process activities on microbial contamination levels.

This combined approach allows for a more effective risk assessment and targeted interventions to control and minimize microbial contamination throughout the manufacturing process.

 

Wednesday, November 15, 2023

Cleanroom Recovery Tests

Unveiling the Intricacies of Cleanroom Recovery Tests: A Comprehensive Exploration

Cleanrooms, the bastions of controlled environments, play a pivotal role in diverse industries such as pharmaceuticals, microelectronics, and biotechnology. Maintaining the utmost cleanliness within these controlled spaces is not merely a standard but a necessity. The ISO 14644-3 Cleanroom Recovery Test, a critical aspect of quality assurance, stands as a beacon in ensuring the resilience of cleanrooms against aerosol particle challenges.

Introduction to Cleanroom Recovery Test

In the realm of cleanroom management, the ISO 14644-3 Cleanroom Recovery Test serves as a litmus test, gauging the ability of these environments to rebound from disruptions. The test, often conducted with precision instruments like the MET ONE 3400+, delves into the recovery capability of cleanrooms when confronted with aerosol particle concentrations.

Deciphering ISO 14644-1 Cleanroom Classification

To understand the significance of the recovery test, one must first navigate through the intricacies of ISO 14644-1. This standard classifies cleanrooms based on air cleanliness, delineating maximum particle concentrations at varying sizes. These classifications are contextualized in "as built," "at rest," and "in operation" states, forming the foundation for subsequent evaluations.

The Cleanroom Recovery Test Journey

Purpose and Methodology

The primary objective of the Cleanroom Recovery Test is to ascertain the duration required for a cleanroom to recover from a challenge concentration to a specified Target Cleanliness Level. ISO 14644-3 emphasizes the application of this test to non-unidirectional airflow systems, preferably during the as-built or at-rest state.

Exclusions and Caution

Notably, the test is discouraged in production settings, and ISO Class 8 or ISO Class 9 environments are deemed unsuitable due to the impractical challenge concentrations. A crucial cautionary note is sounded against residue contamination, emphasizing the need to strike a balance between an effective challenge and the risk posed.

The Enigmatic Target Cleanliness Level

One of the puzzles that the ISO 14644-3 test presents is the selection of the Target Cleanliness Level. Contrary to common misconceptions, this level should not mirror the class limit. Instead, it is recommended to be as low as possible, potentially aligning with the cleanroom's particle baseline but not exceeding 1.5 times that value.

Methods for Evaluating Cleanroom Recovery Performance

ISO 14644-3 outlines two methods for evaluating cleanroom recovery performance: the straightforward 100:1 recovery time method and the alternative "Evaluation by recovery rate." The former, a direct measurement of recovery time, is the preferred and generally achievable approach. The latter serves as a backup, applicable when setting an initial concentration of 100 times the Target Cleanliness Level is unfeasible.

Conclusions and Recommendations

The crux of the matter lies in the propensity of ISO Class cleanrooms to endure unnecessarily high particle concentrations during the recovery test. A case in point is an ISO Class 7 cleanroom challenged with particle concentrations marginally higher than the ISO Class 8 limit. This scenario accentuates the importance of meticulous baseline assessment and prudent selection of the Target Cleanliness Level, facilitating the implementation of the 100:1 Recovery Time method with minimal impact.

The Cleanroom Recovery Test, within the expansive landscape of ISO standards, emerges as a dynamic tool for ensuring the resilience and efficiency of cleanrooms. As industries continue to advance, the meticulous evaluation of cleanroom recovery performance becomes an indispensable aspect of quality assurance, safeguarding the integrity of these controlled environments. In the pursuit of excellence, the ISO 14644-3 Cleanroom Recovery Test stands as a stalwart guardian, ensuring that cleanrooms remain sanctuaries of purity amid the challenges of particle-laden environments.

References

ISO 14644-1: Cleanrooms and associated controlled environments – Part 1: Classification of air cleanliness.

ISO 14644-3: Cleanrooms and associated controlled environments – Part 3: Test methods. First Edition 2005-12-15.