Dr Stefanie Bayer, Labor L+S AG, Germany
Colin Booth, The Binding Site, UK
Arjan Langen, MSD, The Netherlands
Axel Schroeder, Concept Heidelberg, Germany
It is the aim of this course to familiarise responsible personnel from production, quality assurance and engineering with microbiological questions. The participants learn how to interpret microbiological data and which consequences these have for the production.
The quality of drugs and the quality assurance during production are above all determined by their microbiological characteristics. The microbiological requirements on drugs are laid down in various regulations. When an authority inspects a company, it will focus its attention on these and on the requirements made on hygiene.
In their daily work, the responsible personnel in the production units has to understand microbiological results and evaluate their significance for further decisions. However, in practice many microbiological results are misinterpreted and thus often the wrong conclusions are drawn from them. When asked for the most frequent misinterpretations of microbiological results, pharmaceutical microbiologists gave the following answers.
- The difference between bioburden and sterility testing (are they the same?)
- The use of disinfectants guarantees the sterility of the object, surface, culture treated.
- The distribution of microorganisms in a sample or on a surface is uniform.
- Motile microorganisms can swim hundreds of meters in an hour causing contamination problems in remote parts of the facility.
- How can different media formulations give different results?
- Microbial tests described in the Pharmacopoeias can always be validated, no matter what the matrix is, how aggressive it is, e.g. NaOH, how high the concentrations of antibiotics are etc.
- Identification results are absolute and unequivocal, especially when computer-generated.
- Underestimating the importance of cleaning prior to disinfection.
- Environmental monitoring results provide an accurate risk assessment during production.
- How can clean room surfaces not be heavily contaminated when the air counts are out of specification?
- How can endotoxins be present when the bioburden is nil?
- How can the titre of a virus reference standard change according to the detection cell line used?
- WFI is sterile.
- Filters are absolute.
- UV light disinfects and is capable of sterilising surfaces and water.
This listing appears to cover all aspects of microbiology from the interpretation of straightforward issues concerning environmental monitoring, bioburden results and identifications – through to the more complex issues surrounding virology results for the biologics/biotech people.
The misinterpretation of microbiological results often gives rise to the following misunderstandings:
- Huge environmental monitoring programmes (more is better).
- Rejection of batches due to minor out-of- specification results.
- Delayed registration objectives and to attend appeal hearings.
- Numerous contamination incidents due to the application of inappropriate solutions to problems.
- Senseless promises made to regulatory authorities without scientific rationale based on the concept of quality.
This course is designed for responsible personnel from production, quality assurance, regulatory affairs and engineering that has to make judgements, release products and take actions on the basis of the microbiological data supplied.
The Characteristics of Microorganisms
- Cellular organisation, function
- Products; toxins, endotoxins, antibiotics, enzymes
Microbial Identification Techniques
- How it occurs
- What is required for growth?
- Growth kinetics – laboratory culture versus nature
- Effect of stress factors on growth
Detection Methods and Their Limitations
- What is the significance of a name?
- Distribution of microorganisms in nature,
- raw materials and water
- Distribution of microorganisms in pharmaceutical facilities
Cleaning, Sanitation, Disinfection
- What can be detected by: The sterility test, The bioburden test in its various forms. Membrane filtration, pour plate, spread plate,MPN, The test for specified organisms, The endotoxin test
- Limits of detection and factors effecting limits of detection
- Validation of Microbial Test Methods
- Basic principles of validating a microbial test system
- What approaches can you take when a microbial assay test cannot be validated?
- Why cleaning before disinfection?
- The difference between cleaning and disinfection
- Disinfectants and their efficacy
- Methods of disinfection
- Disinfection validation
How To Handle Microbiological OOS Results
- Sampling techniques: air sampling, surfaces, settle plates
- Technical limitations and interpretation of results
- Is there a relationship between high results and contaminated product?
- Typical Out-Of-Specification results: Sterility testing, Bioburden, Endotoxin testing, Cleanroom monitoring
- Investigation of Causal Connection: Laboratory failure investigations, Sampling/process/production failure investigation, Type of microorganisms, Deviations/incidents/assessment, Deviation/investigation report
- Retesting/Reanalysis/Resampling: Definitions, Calculation of mean values, Rejection/Release
- Principles and kinetics of sterilisation
- Selection of sterilisation method
- Types of sterilisation methods
- Validation of the sterilisation process
The objective of these workshop sessions is to give the participants some hands on experience with the fundamentals of microbial techniques and the difficulties associated with interpretation. They will also provide the chance to discuss common problems in an informal atmosphere.
Workshop 1: Hygienic Deviations
Participants will work in small groups on practical case studies of microbiological deviations. They will work on a root cause analysis, and defining corrective and preventive actions.
Workshop 2: Trouble shooting in the microbiological laboratory.
The focus will be on those problems that occur frequently in microbiological quality control. Practicable solution to these challenges will be discussed in small groups.