Periodic Reporting for period 3 - IMPAX (Inline/Instant Measurement for PhArma eXtrusion)
Periodo di rendicontazione: 2018-09-01 al 2019-10-31
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 of Critical Process Parameters which affect Critical Quality Attributes (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 “Industry 4.0” as IMPAX will enable a data-driven pharma manufacturing, contributing to seizing Europe´s chance to assume a leader role in tomorrow´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.
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 of Critical Process Parameters which affect Critical Quality Attributes (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 “Industry 4.0” as IMPAX will enable a data-driven pharma manufacturing, contributing to seizing Europe´s chance to assume a leader role in tomorrow´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.
In the project’s final year, we have produced the following results and highlights. At the beginning of the project, the technology readiness level (TRL) was judged to be at 6. Our aim, at the end of the 3-year development project, was to develop the platform to TRL9. The completion of WP2, 3 and 4 and the key project results below demonstrate that this has indeed been accomplished.
PROJECT RESULTS:
1. Successfully completed external small-scale testing plan (WP4)
2. Successfully completed external large-scale testing plan (WP4)
3. Produced a Technical Case Study on the completed large-scale testing
4. Completed in-house Raman spectrometer prototype
5. Filed two UK patent applications
6. Completion on CFR 21 Part 11 compliant software interface
7. Complete market research & produce a launch plan
NEXT STEPS FOR EXPLOITATION (related to each previous project results, individually):
1. The fully integrated IMPAX prototype was trialled at 6 sites across Europe, using small to medium-scale extrusion systems. Several of these have requested further discussions on commercial terms.
2. The IMPAX prototype was trialled at 1 additional site in Germany using a very large, industrial scale extruder.
3. Distribution of this case-study with ColVisTec’s new IMPAX marketing collateral.
4. The in-house Raman spectrometer module was built and tested. Further refinement is required to match the sensitivity and resolution of the commercially-available alternative.
5. Two patent applications were filed at the UK patent office. The applications will enter international PCT phase in Q1 and Q2 2020.
6. The three spectrometer modules have been successfully integrated into the CFR 21 Part 11 compliant user interface PharmaMV using custom-written OPC-UA protocols.
7. A thorough market analysis was performed, leading to a robust action plan for launch and subsequent marketing of the IMPAX system. This deliverable D5.7 is intended to inform and guide to creation of a go-to-market business plan (D5.8)
PROJECT RESULTS:
1. Successfully completed external small-scale testing plan (WP4)
2. Successfully completed external large-scale testing plan (WP4)
3. Produced a Technical Case Study on the completed large-scale testing
4. Completed in-house Raman spectrometer prototype
5. Filed two UK patent applications
6. Completion on CFR 21 Part 11 compliant software interface
7. Complete market research & produce a launch plan
NEXT STEPS FOR EXPLOITATION (related to each previous project results, individually):
1. The fully integrated IMPAX prototype was trialled at 6 sites across Europe, using small to medium-scale extrusion systems. Several of these have requested further discussions on commercial terms.
2. The IMPAX prototype was trialled at 1 additional site in Germany using a very large, industrial scale extruder.
3. Distribution of this case-study with ColVisTec’s new IMPAX marketing collateral.
4. The in-house Raman spectrometer module was built and tested. Further refinement is required to match the sensitivity and resolution of the commercially-available alternative.
5. Two patent applications were filed at the UK patent office. The applications will enter international PCT phase in Q1 and Q2 2020.
6. The three spectrometer modules have been successfully integrated into the CFR 21 Part 11 compliant user interface PharmaMV using custom-written OPC-UA protocols.
7. A thorough market analysis was performed, leading to a robust action plan for launch and subsequent marketing of the IMPAX system. This deliverable D5.7 is intended to inform and guide to creation of a go-to-market business plan (D5.8)
As IMPAX moved into its 2nd year, a number of important technical milestones were accomplished. Relating to hardware development, the technical team completed the construction of the first prototype and performed tests on its stability, mobility and clean-ability. Thereafter, the installation and integration of the preferred NIR spectrometer and the new bespoke Raman spectrometer were performed. A robust testing plan was produced, setting out the studies required to explore the capabilities and functional limits of the new device. Experimental testing was performed, both in house and with our collaborating partners.
The technical team also worked towards the completion of the new integrated software interface, enabling online and offline data analysis. As this software must be fully compliant with the most recent pharmaceutical manufacturing regulations, we did external software testing and validation, covering user-controls, data-security and data-integrity.
As the IMPAX device became more concrete, dissemination and exploitation were continued and accelerated. A concerted effort to introduce the platform to pharmaceutical companies and CMOs began with attendance at appropriate conferences and manufacturing technology exhibitions. Whilst ColVisTec’s primary focus will be in Europe, we believe it would be remiss not to explore in North American and Asian markets.
The completion of the IMPAX project and the new assets it has afforded, have given ColVisTec opportunities to expand its business across the next three years. Although this is dependent upon attracting further venture finance, the management team fully expects to be able to expand the scientific and sales team over the next six months. Hence, ColVisTec hopes to continue to create highly-skilled jobs for European scientists, engineers and sales professionals.
Finally, through an energetic dissemination campaign, we have tried hard to engage with the pharmaceutical research community, including the rapidly-developing continuous manufacturing sub-section. We believe this has been quite successful and that ColVisTec’s reputation and standing in the field of pharmaceutical extrusion have surely increased. We intend to continue to push for more public engagement and interest in our novel technology and its applications.
The technical team also worked towards the completion of the new integrated software interface, enabling online and offline data analysis. As this software must be fully compliant with the most recent pharmaceutical manufacturing regulations, we did external software testing and validation, covering user-controls, data-security and data-integrity.
As the IMPAX device became more concrete, dissemination and exploitation were continued and accelerated. A concerted effort to introduce the platform to pharmaceutical companies and CMOs began with attendance at appropriate conferences and manufacturing technology exhibitions. Whilst ColVisTec’s primary focus will be in Europe, we believe it would be remiss not to explore in North American and Asian markets.
The completion of the IMPAX project and the new assets it has afforded, have given ColVisTec opportunities to expand its business across the next three years. Although this is dependent upon attracting further venture finance, the management team fully expects to be able to expand the scientific and sales team over the next six months. Hence, ColVisTec hopes to continue to create highly-skilled jobs for European scientists, engineers and sales professionals.
Finally, through an energetic dissemination campaign, we have tried hard to engage with the pharmaceutical research community, including the rapidly-developing continuous manufacturing sub-section. We believe this has been quite successful and that ColVisTec’s reputation and standing in the field of pharmaceutical extrusion have surely increased. We intend to continue to push for more public engagement and interest in our novel technology and its applications.