- Container Closure Integrity during development, qualification and stability testing
- Regulatory, Pharmacopoeial and GMP requirements
- System integrity versus container damages
- Patient risks – do we need batch by batch testing?
- Industrial best practices
Expectations of a GMP-Inspector regarding to Container/Closure Integrity Testing
- Regulatory documents on container / closure integrity testing (an overview)
- Testing methods for CCIT & validation strategies
- Current situation on CCIT in pharmaceutical industry & challenges
- Inspection findings & experience
Overview of Container/Closure Integrity Testing Technologies
The presentation gives a complete overview of the different aspects of leak testing to do CCIT in the pharmaceutical production. The systems presented can be used for the CCIT of vials, ampoules, syringes, BFS, IV bags, blisters etc.
- Leak, leak rate and the relevant physical units
- Leak test methods
- Pressure change methods (vacuum, pressure and LFC)
- Head Space Analysis using TDLAS
- Helium Leak Test and other Mass Spectroscopy Systems
- High Voltage Leak Detection (HVLD)
- Force Sensing Technology
- Capabilities and examples of the different methods
- How to select the right method
- How to generate positive controls
Case Study: 100% Testing of Vials
- System setup
- Validation
- Routine operation
100% inline CCI Testing of Ampoules
- High Voltage inline testing: method description
- Integration in the production process
- Limits of the system
- Qualification of the system
- Validation
- Routine Operation
Integrity Testing of Prefilled Syringes
- Sampling plan
- He-leak testing
- Limitations of the He-leakage test
- Cross validation with mCCI
Visual Inspection Systems
Regulatory Requirements for the Visual Inspection of Parenterals
- Compendial Requirements
- 100% visual inspection & AQL testing
- PharmEur, USP, JP - similarities and differences
- News from the Annex 1 revison
- Risk Management Considerations
Expectations of a GMP Inspector regarding Visual Inspection
- Regulatory documents on visual inspection of parenterals (an overview)
- Manual inspection, semi-automated inspection (personnel, working place, equipment, training & qualification)
- Automated inspection (incl. validation strategy)
- Routine operations, AQL testing, handling of (r)ejects
- Inspection findings & experience
Manual Visual Inspection – Theory and Practical Aspects
- Probabalistic nature of visual inspection
- Defect categorisation
- Differentiation of test kits for training, qualification and routine
- Qualification and training of personnel
- Standardisation of working conditions in Manual inspection
- Usage of the Knapp and the modified Knapp test
Automated Visual Inspection – from Setup to Routine Use
- Limitations of automated inspection
- Setting up a qualification strategy for automated systems
- Cross validation during the PQ phase of an automated system
- Importance of particle detection rates
- System suitability, requalification and revalidation
- Inspection of eject fractions
- The Roche Inspection systems: manual, semi-automated and fully automated inspection
Requirements, Composition, and Handling of
- Test Sets
- Definition of defect categories
- Set-up and composition of a test set
- Test sets and their use for training, qualification and routine
- Handling and release of test sets
- Documentation
Handling Inherent Particulate Matter of Biologics
- in Visual Inspection
- Challenge of inherent particulate matter in drug product solution
- Appearance and characteristics of inherent particulate matter
- Impact on visual inspection
- Handling inherent particulate matter in routine visual inspection
- Establishment of a life-cycle management approach
Re-Inspection of Defect Fractions in
- Visual Inspection
- Different scenarios will be covered such as:
- Re-inspection or additional inspection of “grey-channel” units from (semi-) automated inspection
- Re-inspection in case of exceeding alert limits or
- AQL failures
- Focused re-inspection
- Inspection approaches in case of investigations due to unexpected particles (e.g., to determine frequency of occurrence of visible particles when particles are found during release/stability testing
Automated Visual Inspection Based on Unsupervised Machine Learning
- Vector segmentation using unsupervised machine learning
- Characterizing variation using computer vision
- Learning normal variation in defect-free bottles
- Visual inspection via anomaly detection
Particle Testing and the Correlation with Trending and Batch Release
- Why do we Monitor (What is it all about)
- Data and measurement
- The AQL trap
- Improvement process map
- Investigation and routine analysis,
- Release Process. “To AQL or not to AQL that is the Question”
- Product release: “Falling off a log”