Environmental Monitoring & Process Simulation/Media Fill

Programme

Environmental Monitoring
Why do we do it - what does it tell us

Relevant Guidelines
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
Validation
Drying Issues
Where to place them?
Active Air Sampling
Equipment options / comparison
Validation
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
Limitations
Validation?
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 Methods
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

Process Simulation/Media Fill
Media Fills - The Essential Background
Regulations affecting aseptic manufacture
EU GMP Guide Annex 1
FDA Aseptic Guide
PIC/S Guide 'Recommendations on the Validation of Aseptic Processes'
What media fills consist of (in principle)

Media Fills - How to Design a Media Fill
What medium?
How many units?
How long?
Interventions?
Personnel?

Media Fills - The Involvement of the Microbiology Lab
Why we use TSB
Limitations
BSE/TSE-free ?
Problems with TSB
Contamination of the dehydrated medium (Bacillus)
Issue with Mycoplasma
Irradiated dehydrate (effects of irradiation on growth)
Growth Support Checks
Pharmacopoeial organisms
Local isolates
Preparation of Cultures
Incubation temperatures
Inverting units during incubation
Aerobic vs. anaerobic media fills
Incubation and inspection

QA Oversight
Regulatory background
QA Oversight during Media Fill versus QA Oversight during routine production
How to perform QA Oversight?
Interpretation of QA Oversight results

Media Fills and Personnel
Training and qualifying personnel for aseptic manufacture through media fill
Maintaining qualification
Regulatory requirements

Media Fills and Environmental Monitoring
Environmental monitoring activities during Media Fills
Handling deviations

Media Fills - Handling the outputs
Limits (practicalities and impracticalities)
Handling failures

Media Fill - Identification of contaminating
microorganisms
What the regulators expect
Likely contaminants, unlikely contaminants !!
Isolating contaminating micro-organisms
Identification methods, including genetic
Mycoplasma contamination
What the identification tells you about the process.

Regulatory Problems with Media Fills
What the regulators expect
Examples from Warning Letters
Examples from 483's

Workshop
Managing Interventions
Different kinds of interventions
Selection of interventions for media fills
Selection of interventions for personal qualification
Tracking of interventions between media fills
Assessment of interventions
This workshop involves participants in the issues to be resolved in the identification and management of interventions during media fills in order to answer the demand from the regulatory inspector - "what's the name of the person making that intervention, please show me the evidence from media fills that she has been qualified to perform it"

Workshop
Handling a Media Fill Failure
Types of failures
Evaluation of failures
Documentation requirements
The current regulations on media fills include strict acceptance criteria. But how do out-of-specification results and failures during media fills have to be handled? Which consequences does a media fill failure have? In this workshop, the participants learn how failures have to be evaluated and which consequences they have.