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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - IMPAX (Inline/Instant Measurement for PhArma eXtrusion)

Teaser

Summary

Increasing production costs and competition from lower cost economies make it increasingly difficult for Pharma companies in Europe to manufacture cost effective products. The trend is for European Pharma manufacturers to disinvest in Europe and set up production facilities in lower cost countries. While still being a leading industry, key production equipment suppliers have suffered job losses (and bankruptcy) over recent years. The emphasis in European Pharma is therefore on reducing production costs and investing in more-effective, more-responsive, and innovative manufacturing technologies.
One such early trend is the innovative Continuous Manufacturing (CM) in place of traditional Batch Manufacturing. Extruder-based production is currently one of the most widely used CM techniques, within plastics manufacturing and it is extensively applied in the food processing industry, and it is now beginning to be applied in Pharma for a wide variety of dosage forms and formulations, including: granules, pellets, tablets, capsules, implants, transdermal systems and ophthalmic inserts. Active pharmaceutical ingredients (APIs) are embedded in a carrier, containing meltable materials and additional (inactive) excipients. As pharmaceuticals become more sophisticated with a higher specificity and less side effects, their solubility and therefore their bioavailability suffers. CM extruder processes such as Hot Melt Extrusion (HME) and Wet Granulation (WG) significantly outperform current conventional methodology in offering the possibility of forming solid dispersions with improved bioavailability.
The implementation of HME/WG will be greatly aided by the better availability of inline monitoring tools: The technological basis for CM is the use of Process Analytical Technology (PAT), a mechanism to design, analyse, and control pharmaceutical manufacturing processes through the measurement ofÂ Critical Process Parameters which affectÂ Critical Quality AttributesÂ (CQA). Previously, it was virtually impossible to determine the clinical efficacy of an API online. This made the control and optimization of processes more difficult, as laboratory tests usually take a long time. PAT closes this information gap as data is collected directly in the process in real-time and allows instant corrections and automation. Tools for analysis improve the manufacturers understanding and control of the process, increase process quality, and reduce the risk of losing products due to nonconformity. Moreover this approach aligns with the EU strategy to attain a leadership position in the â€œIndustry 4.0â€ as IMPAX will enable a data-driven pharma manufacturing, contributing to seizing EuropeÂ´s chance to assume a leader role in tomorrowÂ´s digital economy.
The overall objectives of IMPAX are:
1. Contributing to the uptake of the HME/WG in the Pharma industry by engineering the multi-spectra platform
2. Demonstrating quality and bankability of the IMPAX platform through validation with Pharma End-users
3. Introducing the platform in the Pharma market.

Work performed

1. Completion of the device exterior design (including materials selection, surface & shape optimization, optimized connectivity)
A design blueprint for the IMPAX device was generated following several iterative steps, which involved consulatation with potential customers and experienced pharmaceutical manufacturing personnel.

2. Selection of preferred NIR spectrometer device, following substantial in house suitability testing
Several commercially-available NIR spectrometer modules were studied for their flexibility and ease of integration. A preferred model was selected and has been purchased. The next stage is integration of the device into the IMPAX prototype.

3. Development of optical beam-splitter device, which will enable optical fibres to be shared across spectrometer units
By reviewing the current probe design and combining therein our latest ideas for optical fibre sharing, it may be possible to reduce the number of probes needed, thus simplifying operation and reducing costs.

4. Studied methods to prevent optical probe-fouling
Although ColVisTecâ€™s probes are already constructed from cGMP-compliant, anti-fouling materials, the direct contact operability of the probe brings with it the risk of uncontrolled or cumulative surface-fouling. Following experimental studies involving alternative probe materials and surface treatments, the technical team has developed a potentially novel solution to this problem.

5. Patent search performed for novel in situ optical probe cleaning methods
In parallel to the aforementioned design work in self-cleaning optical probes, a wide patent search was performed to identify similar technologies or applications.

6. Development and successful test of new SpecViewer software module
SpecViewer is a software module that enables pharmaceutical manufacturing operators to visualize and quantify spectral details during or after a manufacturing process. The new programme is designed to run alongside and support the EquiColor process monitoring software. The first live test of SpecViewer was performed in Q2 2017 in collaboration with De Montfort University and Astra Zeneca

Final results

As IMPAX moves into its 2nd year, a number of important technical milestones lie ahead. Relating to hardware development, the technical team will complete construction of the first prototype and perform tests on its stability, mobility and clean-ability. Thereafter, the installation and integration of the preferred NIR spectrometer and the new bespoke Raman spectrometer will be performed. A robust testing plan will be produced, setting out the studies required to explore the capabilities and functional limits of the new device. Experimental testing will be performed, both in house and with our collaborating partners.
Whilst hardware optimization and testing is ongoing, the technical team will also be working to complete the new integrated software interface, which will enable online and offline data analysis. As this software must be fully compliant with the most recent pharmaceutical manufacturing regulations, we envisage a period of external software testing and validation, covering user-controls, data-security and data-integrity.
As the IMPAX device becomes more concrete, dissemination and exploitation will continue and accelerate. A concerted effort to introduce the platform to pharmaceutical companies and CMOs will begin with attendance at appropriate conferences and manufacturing technology exhibitions. Whilst ColVisTecâ€™s primary focus will be in Europe, we believe it would be remiss not to explore in North American and Asian markets.
As stated, the successful completion of IMPAX will push ColVisTec forward and into a technology leadership position. This will result in further growth for the SME in Germany, both in revenues and employment. ColVisTec also aims to positively disrupt the pharmaceutical manufacturing sector with the IMPAX product by offering flexible tools to improve operating efficiencies by decreasing waste and increasing process up-time. One of the purposes of continuous pharmaceutical manufacture is to reduce the time and costs that come with off-line quality analysis & assurance. By helping to build new, efficient continuous processes with in-line quality measurement, the IMPAX system will enable these savings and thereby improve the competitiveness of European pharmaceutical manufacturing.