In drug manufacturing, production takes place in controlled environments. The objective is to maintain the quality, safety and effectiveness of the medicines produced by minimizing the risks of contamination.
In these environments, levels of airborne particles are strictly controlled. Manufacturers also design and monitor controlled environments to minimize the presence of microorganisms and bacteria, including through rigorous cleaning and disinfection procedures.
The EU GMPs define the good practices to be put in place for manufacturers. Biocleaning appears to be a critical production step to eliminate waste and particulate, biological and chemical contaminants deposited on surfaces. In the overall biocleaning process, ASD (airborne surface disinfection) contributes to disinfection. The reform of Annex 1 of good manufacturing practices even makes it an essential element.
In this article, you will discover what ASD is and its importance in complying with GMP. We also present Stérigène solutions in terms of ASD.
ASD, a key element of biocleaning
The goal of biocleaning
Biocleaning consists of restoring cleanliness to equipment or premises:
- Following production anomalies (emergency activity)
- Between 2 batches or according to a planned schedule (planned activity)
It brings together a series of steps aimed at eliminating/reducing contaminants in the production environment to:
- Obtain visually clean surfaces
- Make the particle load acceptable according to the class of the zone
- Make the microbial load acceptable according to the class of the zone
“Acceptable” particulate and microbial concentrations are defined in Annex 1 of EU GMP, updated in August 2022.
In accordance with GMP, the manufacturer is required to carry out continuous monitoring of its production environments to keep contamination below the thresholds corresponding to the defined class.
A production stage supervised by GMP
The revision of Annex 1 of GMP requires manufacturers to:
- Adopt a clear and concise contamination control strategy
- Adopt a defined quality system based on the principle of Quality Risk Management
In other words, the manufacturer must assess the risks inherent in its production environments and processes, then implement means to reduce these risks. To this end, GMPs provide guidelines to help stakeholders identify, scientifically evaluate and control all potential risks during the process.
Compared to the previous version of GMP, the revision of Annex 1 increases the requirements for biocleaning. To become compliant, we now recommend following 8 steps:
- Roughing: Removal of visible manufacturing waste to facilitate subsequent cleaning
- Dust removal: particle and chemical decontamination by vacuuming or wet sweeping
- Washing/detergency: possible use of detergents to separate contamination from the surface
- Rinse with PPI water when using detergents to suspend residues
- Scraping: mechanical action to remove residue
- Disinfection to eliminate/reduce microorganisms
- Rinse with PPI water if necessary
- Scraping if rinsing to eliminate disinfectant residues
What do GMPs say about disinfection?
The revision of Annex 1 of GMP provides clear guidance on disinfection expectations.
Article 4.33 provides several clarifications:
- Disinfection must be based on a formalized program
- Prior cleaning should be carried out to remove surface contamination
- More than one type of disinfectant agent should be used
- Disinfection should include periodic use of a sporicidal agent
Further on, the text provides important additions. The process must take into account the appropriate contact time and the manner and surfaces on which the disinfectants are used. Regular monitoring is expected to ensure the effectiveness of the process. And cleaning programs must effectively remove disinfectant residue.
Finally, for the first time, DSVA is explicitly cited in the text as good practice in disinfection.
