Colin Booth, QMS - Quality Microbiology Solutions, UK
Christopher Randell, Sauflon CL Ltd
Dr Björn Wiese, Zimmer GmbH, Switzerland
Environmental monitoring is one of the systems that decide about the product quality in the manufacture of sterile medicinal products. Both European and American GMP regulations place special focus on this topic.
The USP 1116 and especially the FDA’s “Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice“ deal in detail with environmental monitoring.
However, many of the requirements laid down in these documents seem to be excessive for everyday practice on the one hand and leave great scope for interpretation on the other hand.
In practice, environmental monitoring programmes sometimes develop into time-consuming, cost- and personnel-intensive measures. Therefore, it is the aim of this course to provide the participants with pragmatic recommendations for the creation and implementation of environmental monitoring programmes.
Within the framework of this course, the participants are confronted with current hot topics, like:
- Alert / action levels
- Relationship to batch release
- Locations and frequency
- Identification of isolates
- Sampling procedures
and get to know solutions for their own company practice.
This Education Course is directed at staff from Production, Quality Assurance and Quality Control who is responsible for the planning and implementation of environmental monitoring programmes.
Why do we do it – what does it tell us
- EU-GMP Guide Annex 1
- USP <1116>
- FDA Aseptic Processing Guide
- ISO 14644 and ISO13824
- An overview about the most important guidances
We are confronted with a wealth of environmental monitoring guidelines, which means that we are sometimes faced with conflicting specifications and classifications. Which one(s) should I follow? The objective of this session is to review the key points of the guidelines and to apply a common sense approach to their application to your facility and processes.
Non-viable (particulate) Air Monitoring
- The grading of areas for manufacture of sterile medicinal products in the EU
- How to claim classification of areas to current standards
- How to ensure continuing compliance with the classification
- Selection of sampling locations for qualification and routine
- Particle monitoring, how and how often
- Handling the data
This session addresses non-viable (particulate) monitoring in the context of the manufacture of sterile medicinal products. It highlights the current regulations and standards in Europe and the USA, explains why these requirements have been put in place, and describes how to comply with them.
Viable Air Monitoring
- Regulatory Standards
- Settle Plates
- Drying Issues
- Where to place them?
- Active Air Sampling
- Equipment options / comparison
- Where to place them?
Viable air monitoring gives a snapshot in time of the microbiological status of a clean room. Current debates centre on the value of settle plates vs. active air monitoring. In this presentation we will evaluate both types in detail and establish when best and how to use them as part of your environmental monitoring programme.
Surface / Personnel Monitoring
- Surface: How?
- Surface sampling techniques
- Personnel: When and how?
- Results and specifications
- How to deal with shedders/pathogen carriers
Surface sampling techniques give a qualitative indication of surface cleanliness, their limitations should be understood before the results can be meaningfully interpreted. The question of validating recovery has often been raised but it is a question of trying to validate the impossible. Personnel are without doubt the major source of contamination in a clean room environment and are therefore the major hazard to aseptic process. Personnel monitoring is obviously of value in assessing contamination risks. The questions in personnel monitoring are basically when and how? There is the potential that the monitoring interventions do more harm than good and the results generated are valueless for risk assessment purposes but are very useful for pressurising QA personnel. The intention in this session is how to achieve results of real value from your surface and personnel monitoring programme.
Case Study: Trending of Environmental Monitoring Data
- What is a trend?
- How can I use electronic systems to track and trend EM data?
- How to get meaningful information from trending
- Alert and action level setting
Using trending as tool for pro-active environmental control measures
This case study will focus on the benefits you can achieve by effective trending of EM data. It will demonstrate the importance of getting the complete picture. Actual examples will show how you can succeed in identifying the root cause of microbiological contaminations.
- Microbiological media, growth requirements
- Identification of isolates
- Validating your methods
- Using rapid identification techniques
- Recovery problems
- Identification to the level of DNA, what value does it bring
Taking microbiological environmental samples is just the first step in your monitoring programme, you now have to grow, isolate and identify the microorganisms that your have collected. This session deals with all the aspects of this process and how to get reliable, consistent results.
Clean Rooms – RABS – Isolator: Points to consider in Environmental Monitoring
- Comparison of the technical concepts
- Validation of microbiological media for the isolator
- Selection of sampling points
- Transfer of microbiological media
- Interpretation of the results and handling of excursions
The requirements on the manufacture of sterile products increase. RABS (Restricted Access Barrier Systems) and isolators represent the state of the art. Which consequences arise for environmental monitoring?
Environmental Monitoring for Non-Steriles
- Why monitor non-sterile areas
- Risk vs impact
- Overview of regulatory position
- Case study
In this session we will discuss the reasons behind environmental monitoring in a non-sterile area. Is it worth doing? Should you do this? Cover potential benefits against the cost, discuss regulatory view-point, and provide a case study.
Deviation Management for Environmental Monitoring
- Steps to be taken in case of excursions
- When is an excursion a deviation?
- Comprehensive root cause analysis
- The nasty “re-occurrence”
FDA and other inspectorates frequently observe deficiencies in deviation handling of Environmental and Utility Monitoring. It is crucial to have a well documented, comprehensive process. Finding a clear root cause for microbiological excursions is often not easy and effective measures against re-occurrence are also difficult to define. This session will discuss tools, concepts and examples for compliant deviation management.
Investigations / Documentati
- The information content of “variables” data versus quantitative limits
- Published and practical limits
- The information content of qualitative data
- Communicating with tecnt
The final session of the programme addresses the translation of data from environmental monitoring into information which may be of practical use, add value to the company’s operations and ensure compliance.
Workshop: How to Establish an Environmental Monitoring Programme
- Identifying weaknesses in contamination control systems
- Identifying locations which will provide “early warning”signals of loss of control
- Preparing useful environmental monitoring SOPs
Most personnel in the pharmaceutical industry inherit environmental monitoring programmes from the past and rarely get the opportunity to establish a programme for the regulatory requirements and first principles. This session gives participants hands-on experience of working with the regulations and standards versus simplified but “real-life” situations. It is intended to encourage participants to leave with a new outlook on what is being done in their own facilities with a view to improving compliance
Workshop:Interpretation of OOS Resu
- What is an OOS in environmental monitoring?
- OOS in relation to trends
- How to investigate
- Follow-up and corrective actio
Real life case studies are used to get an insight in how to investigate and handle OOS results in environmental monitoring. After an introduction on the principles, participants have to develop an investigation plan, define corrective actions on the presented cases, and assess the product impact. The workshop is very practical and requires the active participation of the participants.