Colin Booth, The Binding Site, UK
Natasha Pain, Lonza Pharma & Biotech, Tokyo, Japan
Alexandra Stärk, Novartis Pharma
During this course you will learn in lectures and workshops
- How to plan a media fill in compliance with European and US GMP requirements,
- How to interpret the results of a media fill,
- How to investigate deviations and define follow-up measures and
- How QA should be involved
In the aseptic processing of medicinal products, the product quality usually cannot be ensured by means of lab controls of the final product. Process validation by means of media fills is the only way to furnish proof of product safety, which is why it justly is the focus of regulatory requirements and official inspections.
A number of revised and harmonised international regulations, especially the FDA Guidance for Industry „Sterile Drug Products Produced by Aseptic Processing“, the EU GMP Guide Annex 1, ISO 13408 and the PIC/S Guide „Recommendation on the Validation of Aseptic Processes”, define highly detailed requirements, the implementation of which is critically examined within the framework of official inspections.
In general, the required media fills should be able to simulate both routine operation and worst-case conditions.
In practice, the question of practicability often arises. How should the requirements be interpreted and how can they be implemented even for special production processes or dosage forms?
This Education course is directed at staff from Production, Quality Assurance, Microbiological Quality Control who are responsible for the planning and evaluation of Process Simulation (Media fill) programmes.
It is also valuable for decision makers who have to deal with Process Simulation data within the framework of production release and Aseptic Process validation.
Media Fills – The Essential Background
Media Fills – How to Design a Media Fill
- 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: Specific requirements for isolators and freeze dryers
- What medium?
- How many units?
- How long?
- 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
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
- 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
Media Fills and Personnel
- Holding times
- Container / Closure integrity after Media Fills
- Holding Tanks
Media Fills and Environmental Monitoring
- Training and qualifying personnel for aseptic manufacture through media fill
- Maintaining qualification
- Regulatory requirements
Media as a Source of Mycoplasma Contamination in Process Simulation
- Environmental monitoring activities during Media Fills
- Handling deviations
Media Fills – Handling the outputs
- Mycoplasma myths
- Plant vs animal media
- Process simulations
- Media production
- A new breed of media
Media Fill - Identification of contaminating microorganisms
- Limits (practicalities and impracticalities)
- Handling failures
Regulatory Problems with Media Fills
- 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
Workshop: Managing Interventions
- What the regulators expect
- Examples from Warning Letters
- Examples from 483s
- 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.