
Q&A Summary on Environmental Monitoring and EU Annex 1
At the end of the webinar on environmental monitoring and the EU Annex 1, a series of key questions were addressed regarding the practical implementation of the new guidelines and technological innovations in the pharmaceutical industry. Below is a summary of the most important questions and their respective answers.
If you missed the webinar, you can watch it registering in the following link
Questions and Answers:
Question 1
Do we still need to use paper logbooks to record environmental monitoring results?
While paper logbooks are an accepted practice, they are no longer suitable for today’s pharmaceutical industry. With advancements in technology and stricter data integrity requirements, it is highly recommended to use validated electronic systems that minimize human error and ensure data accuracy and security. Paper records pose compliance risks due to potential errors in transcription and manual data handling.
On the other hand, logbooks should be kept up to date as contingency plans in case the digital system used should fail at some point.
Question 2
Do we really need fungal limits in Grade C and D areas, or are they unnecessary?
Fungi and spore-forming organisms must be strictly avoided in Grade A and B areas. However, in Grade C and D areas, fungi can appear in controlled quantities. It is essential to keep fungal levels under control with appropriate cleaning and disinfection strategies. Specific alert limits for fungi may be helpful in monitoring their presence and preventing them from entering critical areas.
Question 3
Are we moving toward a future without settle plates, using only active air monitoring?
Settle plates are becoming obsolete, especially in Grade A environments, due to their low efficiency in capturing particles and microorganisms. Originally designed for open environments, settle plates do not provide accurate data in controlled environments like cleanrooms. The trend is moving toward continuous active air monitoring systems, which offer higher sensitivity and precision, aligning with current regulatory requirements.
Question 4
Can you recommend any solution for trending and reporting of environmental monitoring data?
For data analysis and management, systems specifically designed for environmental monitoring by professionals with a microbiological background are recommended. These systems allow the integration of both microbiological and total particle data in a unified platform, offering tools for statistical analysis to identify deviations and take timely corrective actions.
Question 5
Are the limits for particles larger than 5 microns reliable, or are they subject to noise in Grade A environments?
Particles larger of 5 micron the limit has to be set by each company. They should be recorded and link any event of peak detection with an event on the machine or production step. It is important to know how we are generating particles during the process.
Question 6
Can we set up alerts and then adjust them according to the criticality of the operations, products, etc.?
Limits should be set according statistical analysis of the data but also using a rational about how critical is the point/room location and also which is the variation from the previous limit. Is some companies do not accept alert reduction greater than 20 % in order to set rational values.
Question 7
How to fix the fungal limits for the grade- C and grade- D? No guidelines speak about that?
In the guidelines, the fungi limits are part of the total aerobic load. The company should define fungi limits based on the production process that occurs in grade C and D, the risk for the product that the presence of fungi would cause and the historical data.
Question 8
Are there standards for the frequency of analysis either for particle count and microbiological monitoring?
The USP <1116> propose a minimum number of frequency according the class and the operations. It is important to know if the activities are for sterile or non sterile production steps. With low frequency of samples, no option to perform statistical results.
Question 9
I want to know if changes from 20 to 29 and 2900 to 2930 at particle limits are meaningful. Because 14644 and GMP annex 1 are different right now. How should we react to that
GMP Annex 1:2022 has aligned its particle classification limits with those of ISO 14644:2015. So now the two documents are aligned and not as you say are different right now.
Question 10
For continuous in process monitoring, if a session is for 4 hours, does the continuous monitoring need to be for 4 hours or only during the most critical aseptic processing activities?
For continuous in process monitoring, if a session is for 4 hours, the continuous monitoring needs to be for 4 hours for air monitoring in grade A, B, C and D.
Question 11
What are your thoughts on BFPC’s (Biofluorescent particle counters) for Grade A monitoring, particularly for gloveless robotic isolators? How to interpret annex one for BFPC’s?
I am very much in favor of BFPC’s (Biofluorescent particle counters) technology for Grade A monitoring, particularly for gloveless robotic isolators. I used and validated it about 25 years ago with success and FDA approval.
As Annex 1:2022 says, after the validation of the technology, you must start collecting the isolator’s Grade A data and following their statistical analysis set the alert levels and action limits without taking into account the table in Annex 1 which refers to traditional methods.
Question 12
What will we have to do if during plate collection, the plate falls down on the floor and media comes out from the plate? Can we clean the surface with disinfectant if the area is under operation?
YES, you can clean and sanitize the surface with the correct and validated detergent and with the correct and validated disinfectant if area is under operation
The Q&A session provided important clarifications regarding current and future practices in environmental monitoring within the pharmaceutical industry. The discussions highlighted the growing need to adopt advanced technologies and risk-based approaches to comply with the EU Annex 1 regulations. Specifically, the move away from inefficient traditional methods like settle plates and the use of validated electronic systems for data management are key to ensuring quality and safety in the production of sterile products.
Gilberto Dalmaso has over 35 years’ experience in pharmaceutical microbiology and sterility assurance. During his distinguished career he led a series of technology-driven process improvements using scientific methods, while achieving GMP compliance and regulatory approvals mainly for aseptic processes and sterile products.
Today Gilberto is the Global Pharma Advisor and Subject Matters Expert for GDM Pharma Consulting. In this role he collaborates and consults with global pharmaceutical companies to develop and implement science-based strategies and processes that utilize Quality by Design (QbD) principles to monitor, control, and improve the chemical, physical, and microbiological state of various production processes.
Having contributed significantly to industry leaders such as Lonza, Qiagen, Roosterbio, Emergent Biosolutions, and CBMG, Alex brings a blend of technical acumen with hands-on expertise. As a career QC scientist and growing compliance expert, she has consistently demonstrated a commitment to operational excellence and continuous improvement.
Alex holds an undergraduate degree in Biochemical Engineering from UMBC and a graduate degree in Biomedical Engineering from Clemson University. Beyond the laboratory, she brings a global perspective, having lived abroad in China, and is fluent in Mandarin Chinese. Alex also enjoys rock climbing and indulges in tabletop gaming.
Gilberto Dalmaso has over 35 years’ experience in pharmaceutical microbiology and sterility assurance. During his distinguished career he led a series of technology-driven process improvements using scientific methods, while achieving GMP compliance and regulatory approvals mainly for aseptic processes and sterile products.
Today Gilberto is the Global Pharma Advisor and Subject Matters Expert for GDM Pharma Consulting. In this role he collaborates and consults with global pharmaceutical companies to develop and implement science-based strategies and processes that utilize Quality by Design (QbD) principles to monitor, control, and improve the chemical, physical, and microbiological state of various production processes.
Having contributed significantly to industry leaders such as Lonza, Qiagen, Roosterbio, Emergent Biosolutions, and CBMG, Alex brings a blend of technical acumen with hands-on expertise. As a career QC scientist and growing compliance expert, she has consistently demonstrated a commitment to operational excellence and continuous improvement.
Alex holds an undergraduate degree in Biochemical Engineering from UMBC and a graduate degree in Biomedical Engineering from Clemson University. Beyond the laboratory, she brings a global perspective, having lived abroad in China, and is fluent in Mandarin Chinese. Alex also enjoys rock climbing and indulges in tabletop gaming.
Gilberto Dalmaso has over 35 years’ experience in pharmaceutical microbiology and sterility assurance. During his distinguished career he led a series of technology-driven process improvements using scientific methods, while achieving GMP compliance and regulatory approvals mainly for aseptic processes and sterile products.
Today Gilberto is the Global Pharma Advisor and Subject Matters Expert for GDM Pharma Consulting. In this role he collaborates and consults with global pharmaceutical companies to develop and implement science-based strategies and processes that utilize Quality by Design (QbD) principles to monitor, control, and improve the chemical, physical, and microbiological state of various production processes.
Having contributed significantly to industry leaders such as Lonza, Qiagen, Roosterbio, Emergent Biosolutions, and CBMG, Alex brings a blend of technical acumen with hands-on expertise. As a career QC scientist and growing compliance expert, she has consistently demonstrated a commitment to operational excellence and continuous improvement.
Alex holds an undergraduate degree in Biochemical Engineering from UMBC and a graduate degree in Biomedical Engineering from Clemson University. Beyond the laboratory, she brings a global perspective, having lived abroad in China, and is fluent in Mandarin Chinese. Alex also enjoys rock climbing and indulges in tabletop gaming.