Christoph Herdlitschka, Wilco
Dr Roman Mathaes, Lonza
Olivier Métraux, F. Hoffmann - La Roche
Dr Tobias Posset, Roche
Dr Heino Prinz, Rommelag AG
Dr Bernd Renger, Immediate Past Chair of the European QP Association
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.
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 vapor 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?
- Will container closure integrity testing change to 100% inline testing?
- Modern blue dye testing
- Which testing technologies are available and suitable?
- CCI testing of prefilled syringes
- CCI testing of lyo & liquid vials
- CCI testing of ampoules
This conference 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.
Container Closure Integrity testing of sterile drug products – requirements, expectations and exaggerations
Overview of container/closure integrity testing technologies
- 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
The presentation gives a comprehensive overview about current CCI technologies and techniques. It focuses in the first part on physical fundamentals of the different testing methods
- Pressure / Vacuum Decay
- LFC (Liquid Filled Container) leak testing
- TDLAS/ HSA (frequency modulated spectroscopy)
- High Voltage leak testing
- 3µm IR and Mass-Spectroscopy
- Force Detection
In the second part criteria or a selection matrix for test methods related to the product requirements and properties including primary container type, product properties (liquid, lyo, etc.) is presented. The main topics here are as follows.
Modern Blue Dye Testing – still the standard CCI method?
- Inline versus sample testing
- Limits and false acceptance traps
- Leak sizes and leak rates (false friends and measurable properties?)
Integrity testing of Prefilled Syringes
- Regulatory requirements and subsequent test method in industry
- Critical method aspects, e.g. process monitoring
- Perspective and limits in context of product life cycle
100 % inline CCI testing of ampoules
- Sampling plan
- He-leak testing
- Limitations of the He-leakage test
- Cross Validation with mCCI
Case Study: 100 % inline testing of Lyo Vials
- High Voltage inline testing: method description
- Integration in the production process
- Limits of the system
- Qualification of the system
- Routine Operation
- System setup
- Routine operation