Control of Parenterals - Container/Closure Integrity Testing & Visual Inspection Systems
Barcelona, Spain
Course No 17272
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Speakers
Dr Martin Becker, IDT Biologika
Martin Dearden, ECA Visual Inspection Group
Dr Helmut Gaus, WinSol, previously Boehringer Ingelheim
Roland Koch, Gasporox
Felix Krumbein, Roche
Christof Langer, OSConsulting
Dr Daniel Müller, GMP-Inspector
Dr Tobias Posset, Roche
Dr Brian Turnquist, Boon Logic
Désirée Womser, Novartis
Martin Dearden, ECA Visual Inspection Group
Dr Helmut Gaus, WinSol, previously Boehringer Ingelheim
Roland Koch, Gasporox
Felix Krumbein, Roche
Christof Langer, OSConsulting
Dr Daniel Müller, GMP-Inspector
Dr Tobias Posset, Roche
Dr Brian Turnquist, Boon Logic
Désirée Womser, Novartis
Objectives
CCI Testing
Different products and different container types require different testing methods: this event aims at giving an overview of the different CCI testing systems which are applied during production and as part of the quality control system. Apart from technical aspects the regulatory requirements on CCI testing will be highlighted as well as the applicability of inline and offline testing.
Visual Inspections Systems
Main topic of this course is the detection of defetcs like particles in injectables and their evaluation during batch release. Besides the current regulatory requirements with regards to particulate matter, routine 100% inspection of injectables will be addressed. Manual inspection as well as automated inspection systems will be covered, including validation, training, defect categories, AQL testing, trending and batch release considerations.
Different products and different container types require different testing methods: this event aims at giving an overview of the different CCI testing systems which are applied during production and as part of the quality control system. Apart from technical aspects the regulatory requirements on CCI testing will be highlighted as well as the applicability of inline and offline testing.
Visual Inspections Systems
Main topic of this course is the detection of defetcs like particles in injectables and their evaluation during batch release. Besides the current regulatory requirements with regards to particulate matter, routine 100% inspection of injectables will be addressed. Manual inspection as well as automated inspection systems will be covered, including validation, training, defect categories, AQL testing, trending and batch release considerations.
Background
CCI Testing
An intact container closure system, which is the sum of packaging components that protect the dosage form, is the pre-requisite for a safe and sterile drug product. The CC system protects the product from microbial contamination and also from exposure to gases or water vapour or the loss of solvent. Container Closure integrity testing is therefore a regulatory requirement and it is part of the whole life cycle of a sterile drug product.
Initially this testing was performed as part of the initial development of the packaging system and the system’s suitability verified in stability studies including on-going stability. Over the years, the expectation was raised to perform batch by batch verification with latest trends to 100% inline or offline testing wherever possible.
We will discuss and answer questions like:
- What are the current and upcoming GMP- and compendial requirements in the US / EU / RoW?
- Will container closure integrity testing change to 100% inline testing?
- What does the Annex 1 require?
- How do we have to define’ tight’?
- Which testing technologies are available and suitable?
- Is blue dye testing still a standard? And how does modern blue dye testing look like?
- CCI testing of prefilled syringes
- CCI testing of lyo & liquid vials
- CCI testing of ampoules
Visual Inspections Systems
In most cases particles found in parenteral medicines will lead to a quarantined product or even to the recall of the product – as we have seen in the last years in the cases of several pharmaceutical companies. Responsible staff in charge will have to start root cause analysis to find the source of the particles and will have to do an evaluation of batches already shipped.
There is still confusion within the global pharmaceutical industry with regard to the requirements for testing for visible particles. After the USP chapters <790> and <1790> were published, things have become much clearer, at least for the US. But still, lots of questions arise, e.g. concerning re-testing, detection capabilities and revalidation of inspection Systems.
Furthermore there has been a recognisable trend towards automated inspection machines throughout the last years. The challenge for pharmaceutical companies is to find a suitable machine for their products and to determine reasonable inspection parameters during qualification and validation. But also during routine process there are questions arising like re-testing and the usage of test-sets, doing AQL-Testing as well as the adjustment of parameters of the vision systems.
There is still confusion within the global pharmaceutical industry with regard to the requirements for testing for visible particles. After the USP chapters <790> and <1790> were published, things have become much clearer, at least for the US. But still, lots of questions arise, e.g. concerning re-testing, detection capabilities and revalidation of inspection Systems.
Furthermore there has been a recognisable trend towards automated inspection machines throughout the last years. The challenge for pharmaceutical companies is to find a suitable machine for their products and to determine reasonable inspection parameters during qualification and validation. But also during routine process there are questions arising like re-testing and the usage of test-sets, doing AQL-Testing as well as the adjustment of parameters of the vision systems.
We will address those topics during the conference and discuss and answer questions on
- The latest compendial requirements concerning particulate matter
- Compliance with the revised Annex 1
- Training and qualification of operators in the manual inspection
- Validation and operation of an automated inspection system
- Trending and monitoring of visual inspection data
- Correct AQL testing as part of the batch release
- Re-inspection of defect fractions
- Usage of artificial intelligence in visual inspection
Target Group
CCI Testing
This course is directed at specialists and executives from the areas engineering and production and QA dealing with the implementation and operation of systems for the container/closure-integrity testing of sterile medicinal products.
Visual Inspections Systems
Visual Inspections Systems
This course is directed at staff from sterile operations, that is production, quality assurance and engineering. But also suppliers of primary packaging materials and inspections technology are target group of this Event.
Best Practice Paper
All participants receive the current version of ECA’s Best Practice Paper on “Visual Inspection” for free.
Programme
Container Closure Integrity Testing of Parenterals
Container Closure Integrity Testing of Sterile Drug Products – Requirements, Expectations and Exaggerations
Container Closure Integrity Testing of Sterile Drug Products – Requirements, Expectations and Exaggerations
- 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
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”
GMP Conferences by Topics
- Quality Assurance
- GMP in Biotechnology
- Microbiology
- Regulatory Affairs
- GMP in Pharmaceutical Development
- Quality Control
- GDP
- Sterile / Aseptic Manufacturing
- Computer Validation
- Validation
- Technical Operations
- GMP for APIs and Excipients
- Medical Devices
- GMP Basic Training Courses
- Packaging
- Data Integrity