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?
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”.
Media Fills: Specific requirements for isolators and freeze dryers
- Media fill design for isolators and freeze dryers
- Special interventions into isolators and freeze dryers
- Validation of standing times for isolators and freeze dryers
- Isolator gloves
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
Discussion of particular issues
- Holding times
- Container / Closure integrity after Media Fills
- Holding Tanks
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 as a Source of Mycoplasma Contamination in Process Simulation
- Mycoplasma myths
- Plant vs animal media
- Process simulations
- Media production
- A new breed of media
Media Fills – Handling the outputs
- Limits (practicalities and impracticalities)
- Handling failures
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.
Media Fill - Identification of contaminating micro-organisms
- 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