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Automatic inspection of lyophilized preparations through innovative ICT control system

Periodic Reporting for period 1 - LYO-CHECK (Automatic inspection of lyophilized preparations through innovative ICT control system)

Reporting period: 2016-11-01 to 2017-10-31

LYO-CHECK is the short name for our project, entitled: “Automatic inspection of lyophilized preparations through innovative ICT control system”.
The aim of the project is to create two machines, one pilot machine and one 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 (which is based on a dedicated software and a dedicated optical layout);
an ancillary technology (head space gas analysis) for testing the sterility of the product via container closure integrity (CCI) inspection.
The project responds to the need of the fast-growing number of pharmaceutical manufacturers who produce lyophilized preparations, providing an innovative automatic inspection machine which will offer consistent and accurate inspection of lyophilized parenteralia products.
The main benefits from employing the LYO-CHECK machine will be:
• 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 versus human behaviour (allowing for a continuous process, also resulting in production cost decrease; see also next point)
• Cost saving for pharma manufacturers
The 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.
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)
Evolved software for image analysis: Several algorithms are 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
The specific objectives and expected outcomes of the project are:
Software improvement and redefinition of the geometry and the type of lighting sources compared to the possible criticism to be traced.
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.
Market strategy and business model plan optimization.
Dissemination and communication. All stakeholders and wider public will know about the LYO-CHECK project and its output product.
During the first 12 months of the project, the design of the pilot machine has been finalized, and the machine has been constructed. Validation tests with artificial samples (test kit) as well as placebo samples from several potential clients have been run ,and the results have shown that the pilot machine is consistent in performance (both from a mechanical point of view and an inspection point of view), which is essential for its validation; besides the accuracy of inspection is very high and the generation of false reject is non-significant thanks to the newly developed optical architecture. A series of new algorithms have also been written to target peculiar defects of the lyo products, such as melt-back, shrinking and irregular morphology of the product surface.
Besides, HSGA technology has been fully studied and after several empirical tests the final hardware and configuration for the future industrial machine has been selected, that is: new-generation laser with optic fiber; single path, double heads, to be installed onto a dedicated arm at the main inspection carousel; all this will allow for multiple measurements which guarantee the utmost precision of the data.
A communication and dissemination plan has been developed, as well as we the specific project website, brochures, poster and all important tools aimed to reach all stakeholders.
From the market analysis and business planning point of view, we can basically confirm the business model and expected results from LYO-CHECK. We have already selected of the trade shows where the machine will be displayed to focus on the target territories, and all Antares’ agents have been informed about the project and received the first training about the pilot machine during internal sessions and events held at Antares headquarters.
The work performed in the first year allows us to be confident about the reaching of the expected impacts, and mostly about the technical impacts which were stated in the proposal phase. In particular, the two patent pending registrations for specific mechanical & optical solutions have proven – during the test with the placebo samples – to be very efficient and have increased the detection rate compared to standard technology. Of course, this will be a boost for the market acceptance of the LYO-CHECK machine and also draw attention for the future industrial one.
Considering that the lyophilized form will become the most widely used in the production of high added-value preparations for injection, the increase in product quality and production output can be achieved only by the combination of different factors and improvement strategies which have been taken into account while designing and developing the LYO-CHECK machine; in particular the new machine for inspection of lyo products will have a strong impact resulting on:
• MORE COST-EFFECTIVE PROCESS: the use of the inspection machine makes the overall process cost effective [VS costs of human operators] with a short payback of the machine and higher accuracy of the inspection itself: then the technology may be applicable also to consumer non-high value products and in both cases reduce the amount of false-rejected unit
• USE DURING NEW DEVELOPMENT STAGE: it is also applicable to product under development and pilot batches necessary for new product registration, speeding up the whole registration process and making it less expensive
• PRICE DECREASE FOR END USER: since the pharmaceutical manufacturers will save money by using the LYO-CHECK machine (as per explanation at the two point above), they have decrease the final price for the public of the product, keeping the same profit on the portfolio pipeline
• ZERO WASTE STRATEGY: enables the reduction of the indirect rejects on secondary packaging operations (due to standard control techniques) since the products have been previously inspected
• PROCESS RE-DESIGN: possibility to rethink the obsolete production and inspection process, linking production directly to secondary packaging → continuous production process
• ROBUSTNESS OF VALIDATION: consistency of results of the automatic machine compared to human ones
OTHER KEY POINTS IN PHARMA MANUFACTURING: such as quality by design, continuous improvement, process automation, will be achieved using the LYO-CHECK Machine