Gabriel Anderson, Novartis
Dr Martin Becker, Siegfried Hameln
Martin Dearden, PaxVax Berna
Dr Helmut Gaus, Winsol, previously Boehringer Ingelheim
Al Goodwin, Amgen
Alan Kelly, Sanofi
Felix Krumbein, Roche
Dr Tobias Posset, Roche
Dr Heino Prinz, Rommelag AG
Christof Langer, OSConsulting
Main topic of this conference is the detection of particles in injectables and their evaluation during batch release and continuous process improvement. 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 training, AQL testing, trending, inspection equipment and batch release considerations.
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.
We will address those topics during the conference and discuss and answer questions on
- The latest compendial requirements concerning particulate matter
- Training in the manual visual inspection
- Qualification and operation of an automated inspection system
- Threshold studies and the border of visibility
- Trending and monitoring of visual inspection data
- Limitations of the AQL test
- New inspection technologies
- Re-inspection of defect fractions
This conference is directed at specialists and executives from sterile operations, that is manufacturing, quality assurance and engineering. But also suppliers of primary packaging materials and inspections technology are target group of this conference.
The Participants of the Particles in Parenterals Conference receive the current version of ECA’s Best Practice Paper on “Visual Inspection” for free!
Pre-Conference Course "Fundamentals of Visual Inspection & AQL Testing"
The training course on visual inspection which takes place the day before the Particles Conference gives you an understanding of the fundamentals of visual inspection of injectable products, applicable to manual and automated inspection. You will also learn how to implement an automated system on the basis of the manual inspection. The course also includes an AQL training, that is you will learn how to use AQL tables to set defect limits and how to evaluate batch inspection data.
For that purpose all participants of the Pre-Conference Course receive the AQL Inspector’s Rule as tool for AQL testing for free.The rule covers a wide range of AQL's with Normal, Tightened and Reduced inspection for both single and double sampling plans according to ISO 2859-1 (1999). The practical usage of this tool will be shown during the course.
Skills you will develop through the course:
Content of the course in detail:
- Ensuring GMPcompliance in manual inspection
- Setting up a qualification strategy for automated systems
- Usage of statistical tools for assessing inspection data
- GMP-compliant routine operation of automated systems
- Requirements of the Pharmacopeia
- Defect categorisation
- Test kits for training, qualification and routine
From Manual to automated inspection
- Qualification and training of personnel
- Standardisation of working conditions
- AQL in the manual inspection
- Usage of the Knapp and the modified Knapp test
- Cross validation during the PQ phase
- Importance of particle detection rates
- System-Suitability, Requalification and revalidation
Dr Helmut Gaus, WinSol & former Director Quality Control at Boehringer Ingelheim
Dr Tobias Posset, Head of Production Support Roche Diagnostics
Particles in Parenterals Conference
Regulatory Requirements for the visual inspection of parenterals
Presentation and discussion of the ECA Best Practice Paper on Visual Inspection
- Compendial Requirements: 100% visual inspection & AQL testing; PharmEur, USP, JP - similarities and differences
- News from the Annex 1 revison
- GMP Expectations: Manual inspection; Automated Inspection
- Risk Management Considerations
Particle testing and the correlation with trending and Batch release
- The best practice paper has been originally developed by the advisory board of the ECA Visual Inspection Group. Much rather than a strict requirement document, this paper is intended to be a reference for controversial issues. The first version of this paper has been published in September 2014 in Copenhagen. It has gained a broad acceptance in the industry afterwards.
- The current version as well as planned updates will be explained and discussed in Hamburg.
Re-inspection of defect fractions in visual inspection
- 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”
Advanced techniques for particle detection and laser inspection process for vial CCIT
- 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 of large volume parenterals – 360 degree approach for container quality control
- Standard machine vision particle detection use only three or four algorithms. Already available and used in multiple industries are powerful algorithms which start to give you more information about the particle that has been detected. Using real case studies it will be shown how these new tools are adopted in the most recent automatic visual systems.
- Present visions inspection systems that are used for CCI checking of vials work with 2D images which are analysed by the vision software. This can lead to false fails because the closure condition is extrapolated from a 2D image. Using more advanced 3D laser profiling results in more human like data available to make judgments. Example what crimp angle is optimal and how far have we crimped the vial. This data is available real time and speeds can match the fastest AVI available at present.
Case Study Sanofi: Manual visual inspection
- A new technique for particle detection in LVP containers will be presented with very low bubble influence combined with detailed detection and monitoring of process related quality aspects for container integrity and cosmetic defects. Includes an outlook using the technique as an application for IV Bags.
Case Study Novartis: Fully automated visual inspection
- Preparation of defect sets
- Sensitivity / threshold studies
- PQ & Knapp-Test studies
- Training and qualification of MVI operators
Manual detection of particles at the border of visibility
- Implementation of the system: Qualification concept, Knapp studies & test sets
- Routine use of the system: AQL testing, Re-inspection, Re-validation of the system
Impact of the Annex 1 revision on the testing of parenterals
- General requirements: USP 1790: Composition of test kits for training, qualification and routine; Inspection conditions (inspection time, illumination, etc.)
- Manual Inspection: Training and qualification of manual operators; Modified Knapp-Test
- Threshold study under different inspection conditions
Visual Inspection and Health Authority Expectations & Observations
- 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
- Observation at the AIM qualification
- Comments to the 5000 test
- Dealing with particles & complaints