Dr Martin Becker, Siegfried Hameln
Klaus Boje, Boehringer Ingelheim
Dr Michael Eakins, Eakins & Associates USP Expert Committee Member
Roland Koch, Wilco
Dr Tobias Posset, Roche
Dr Bernd Renger, ECA & 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 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?
- 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
USP's Approach to Container-Closure Integrity Testing
- 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
Overview of container/closure integrity testing technologies
- Overview of USP chapter <1207>
- CCI definitions and key concepts for sterile drug products
- Leakage concepts
- Regulatory requirements
- Revision of USP chapter <671>: CCI for solid oral dosage forms
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.
Modern Blue Dye Testing – still the standard CCI method?
- 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
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
Impact of the Annex 1 revision on the testing of parenterals
- System setup
- Routine operation
- The final draft for comments of Annex 1
- Contamination Control Strategy
- New requirements on process simulation
- Container Closure Integrity requirements
- New expectations on Visual Inspection