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Automatic inspection of lyophilized preparations through innovative ICT control system

Periodic Reporting for period 2 - LYO-CHECK (Automatic inspection of lyophilized preparations through innovative ICT control system)

Reporting period: 2017-11-01 to 2018-10-31

LYO-CHECK is the short name of our SME-INSTRUMENT phase 2 project titled “Automatic inspection of lyophilized preparations through innovative ICT control system”, which ended in October 2018. This two-year EU-funded project delivered an innovative fully automatic industrial machine for the inspection of lyophilized pharmaceutical preparations intended for injection, based on the two key elements of:
- an innovative vision architecture and dedicated suite of algorithms for inspection
- addition of head space gas analysis (HSGA), for testing the sterility of the product via container closure integrity inspection.
The output machine responds to the need of the fast-growing number of pharmaceutical manufacturers who produce lyophilized preparations, providing an innovative automatic inspection tool which allows consistent and accurate inspection of lyophilized parenteralia products.
Starting from Antares Vision’s intermittent inspection machine and its know-how about the inspection of liquid formulations, a “pilot” LYO-CHECK machine has been developed and tested during the first year of the project, embedding new patented solution for lighting architecture and a new suite of algorithms dedicated to specific lyo product inspection. During the second year, the pilot machine has been further optimized and upscaled to the fully automated industrial version (which higher production output), which has been improved with additional inspection stations and implemented with the ancillary technology of the HSGA to test the container closure integrity. The HSGA has been finally configured with a new-generation laser optic fiber, single-path and double heads, installed at the lower arm of the main inspection carousel .
The specific activities have been focused on:
• Software improvement and creation of a dedicated platform and library for the lyo products inspection along with the redefinition of the geometry and the type of lighting sources compared to the possible criticism to be traced, necessary to obtain perfect pictures.
• Assembly of a single equipment that performs the function of both visual inspection and check of the vial integrity thanks to the ancillary technology HSGA. The innovative machine has been be scaled-up and demonstrated.
• Market strategy and business model plan optimization. The product (the “pilot” machine) was ready for market uptake and commercialization within the first year of project end and has been used both for feasibility tests simulation real production/inspection conditions and also it was taken to main trade shows for live demonstrations to all potential customers.
• Dissemination and communication. All stakeholders and wider public did know about the LYO-CHECK project and its outcomes.
The LYO-CHECK machines key technological elements are:
• Transferring and Manipulation System: A sophisticated mechanical handling is fundamental in order to avoid damage of the inspected products as well as to ensure the acquisition of the best-possible image. In fact, if the product is not properly transferred in front of the cameras, the captured images would be poor in quality and details, and this would impair a correct analysis. Perfect manipulation also allows for high speed which is essential to cope with high production capacity. This was achieved via: split in-feeding screw, guideless starwheels with vacuum suckers, newly designed lighter grippers to be used in the main inspection carousel
• Lighting source and positioning: Lighting techniques are fundamental for the correct detection of possible defects which, most of the times, are hardly noticeable with the naked eye. The task of a proper lighting system is to enhance the presence of possible defects on the surface of the product, optimizing the environment. This is also defined as “optical architecture” which includes the matching with a specific type of camera, its location towards the object to be pictured and the time the light is set on (Antares uses light in a strobed way). Two brand-new configurations were industrialised and protected with a patent application for – respectively – the inspection of the lyo cake morphology and presence/absence of foreign matters; the quality of the crimping of each product unit.
• Evolved software for image analysis: Several algorithms do run in parallel to ensure the utmost security of the good/bad decision and to enable a quick analysis. Advanced algorithms are created to backtrack the sensitivity of the acceptance thresholds and optimize them, in order to minimize false reject rate and therefore to move the bar of inspection from probabilistic to deterministic. A new suite of algorithms has been created to inspect peculiar defects of the lyo products (such as shrinking, foam area) as well as to run the new inspection stations created for the INDUSTRIAL LYO-CHECK Machine, i.e. glass vial shoulder inspection; rubber stopper inspection; glass vial heel inspection.
Pharmaceutical products intended for injection, also called PARENTERALIA, are becoming more and more commonly found in lyophilized form and this trend appears to grow steadily, especially for anti-infectives, biotechnology derived products, and in-vitro diagnostics.
The quality-control inspection of products in lyophilized form pose peculiar challenges, needing a dedicated system which is totally different from the one so far applied to inspect parenteral products in liquid form. For this purpose, it is of the utmost importance:
• To control the products, and to prepare a “defects catalogue”;
• To reduce the number of “false rejects”- aspect connected especially to the manual inspection and sorting of the product that seriously compromises the productivity of the line and that the manufacturer has to face and manage. False rejects are due to many incidental variables that could distort the operator judgment such as:
o adherent powder inside the bottle that “shields” the vision;
o surface crack on cake that creates shadows potentially confused with impurities;
o irregularities of the wall density of the glass vial which create reflections and / or “shadow zones“.
In response to these needs, the LYO-CHECK machine provides consistent and accurate inspection of lyophilized parenteralia products resulting in:
• Higher quality of the overall production batch (all defective units will be found, tracked and rejected)
• Increased patient safety (no defective units will reach the hospitals)
• Stronger validation procedure for pharma manufacturers due to consistency of the machine performance vs human behaviour (allowing for a continuous process, also resulting in production cost decrease)
• Cost saving for pharma manufacturers.