Periodic Reporting for period 1 - Classizer (A novel and revolutionary instrument for the classification and sizing of micro-” and nano- particles in biological, industrial and environmental complex fluids.)
Reporting period: 2017-08-01 to 2018-01-31
Summary of the context and overall objectives of the project
Classizer™ is the right response to the need for a reliable, relevant, and real-time particle analysis.
We created Classizer™ as the reference technology and solution for particle analysis of complex fluid and with the aim to offer to the industry players a game-change device for maximizing their costs. Classizer™ can compete with and outperform the present instruments on market. SPES technology is forecasted to speed up the R&D, production and QC processes of novel products based on micro and nanoparticles, thus paving the way for the market of smart micro and nano-materials in key fields such as pharmaceutical, cosmetic, nutraceutical industries.
We started from the observation that particle size analyser available on the market are usually based on light scattering methods which present limits due to the severe assumptions on which they are based. An incomplete and misrepresented characterisation of micro and nanoparticles forecloses the fully exploitation of systems as drug delivery, anti - tumoral drugs and smart healthcare, all areas presenting enormous business prospective as well as clear benefits for European citizens with the potential access to novel therapies and solutions. The emerging role of novel products based on micro and nanoparticles in markets as different as pharmaceuticals and cosmetics, pigments and agro-pharma, ceramics and electronics increasingly demands adequate technologies for a complete, fast, cheap and accurate particle characterisation, as request from regulatory agencies. This is fundamental to fulfil the R&D process as well as Quality Control (QC), especially where complex fluids are involved. What is more, in the construction industry, for instance, cement producers have found that switching from a conventional fineness measurement technique to particle size analysis provides more sensitive cement characterisation and better parameters for tuning product performance. So, real-time analysis is not possible because measurement times are too long; accuracy reduces at higher values, for example for finer cements. The main need from the different industry sectors is for micro and nanoparticle characterisation in a cheaper, faster, more reliable and more informative way.
A vast number of industries rely on particle size as a critical process and it stands as a crucial step for the manufacturing of several products such inks (it determines the appearance and gloss of paint; the reflectivity of highway paint), cement (it fixes upon hydration rate & strength of cement properties), pharmaceuticals, food (it decides the flavor of cocoa powder), make-up (it determines the appearances of cosmetics). Particle size is thus a key factor in several - and more and more increasing - industrial sector and development/manufacturing proceedings such as crushing, homogenization, emulsification, micro-fluidization when lab measurements are needed to track changes in particle size. This is particularly true for the pharmaceutical industry, where the size of active ingredients influences critical characteristics such as content uniformity, dissolution and absorption rates. Here, the so-called nano-biotechnology is key for competing onto the market: the convergence of nanotechnology and biotechnology, and in particular its applications in the medical sector are considered as one of the most promising and most advanced areas of nanotechnology in the EU and beyond. In fact, commercialisation efforts in nano-medicine are picking up worldwide. Over the past two decades scientists have learned to design, manufacture and manipulate nanoscale materials. At the point where nano-materials meet with a molecular understanding of cell function and disease development, nano-medicine emerges. Using nano-materials allows to target cancerous tissue, to transport drugs and imaging agents into cells or to stimulate cell responses supporting the healing process. For these applications nano-materials are unique as their scale corresponds to the scale of biomolecules and it is intuitively understandable that nano-materials could potentially be of great value for medical applications. The Global Nanotechnology Market is poised to grow at a CAGR of around 18.1% over the next decade to reach approximately $173.95 billion by 2025 and this represents a huge opportunity for the EU to boost the competitiveness of both large and SMEs in the sector, with large positive impact on the EU economy.
Classizer™ project can make the difference by introducing something new to Europe and beyond in terms of technology applied to particle size. Our solution can effectively meet the end-users/customers needs for accurate, real-time information for particle size bringing maximizing the costs and offering reliable and trusted information. As resulted from the market analysis (Section 2), this aspect becomes crucial in any growing market, EU included. We will take advantage of EU present needs building on the fact that present technologies for particle size, in particular addressed to complex fluid, suffer from data measurement incoherences, so our superior class device paired with a novel technology will represent the right solution at the right time for the industry
Our final scope is to introduce Classizer™ into the market our SPES. This will pass through the following strategic/operational business objectives:
1. To optimise our particle size analyser for introduction onto the Market
2. Set up partnerships with industrial partners, stakeholders, improving market research outcomes
3. Set up pilot actions to test our device in at least 3 different countries (already identified), with micro-targeted users
4. Achieve standards compliance; implement a sound IPR strategy basing on the results achieved during the pilots
5. Establish the full value chain, sales strategy, reducing time-to-first sell
We created Classizer™ as the reference technology and solution for particle analysis of complex fluid and with the aim to offer to the industry players a game-change device for maximizing their costs. Classizer™ can compete with and outperform the present instruments on market. SPES technology is forecasted to speed up the R&D, production and QC processes of novel products based on micro and nanoparticles, thus paving the way for the market of smart micro and nano-materials in key fields such as pharmaceutical, cosmetic, nutraceutical industries.
We started from the observation that particle size analyser available on the market are usually based on light scattering methods which present limits due to the severe assumptions on which they are based. An incomplete and misrepresented characterisation of micro and nanoparticles forecloses the fully exploitation of systems as drug delivery, anti - tumoral drugs and smart healthcare, all areas presenting enormous business prospective as well as clear benefits for European citizens with the potential access to novel therapies and solutions. The emerging role of novel products based on micro and nanoparticles in markets as different as pharmaceuticals and cosmetics, pigments and agro-pharma, ceramics and electronics increasingly demands adequate technologies for a complete, fast, cheap and accurate particle characterisation, as request from regulatory agencies. This is fundamental to fulfil the R&D process as well as Quality Control (QC), especially where complex fluids are involved. What is more, in the construction industry, for instance, cement producers have found that switching from a conventional fineness measurement technique to particle size analysis provides more sensitive cement characterisation and better parameters for tuning product performance. So, real-time analysis is not possible because measurement times are too long; accuracy reduces at higher values, for example for finer cements. The main need from the different industry sectors is for micro and nanoparticle characterisation in a cheaper, faster, more reliable and more informative way.
A vast number of industries rely on particle size as a critical process and it stands as a crucial step for the manufacturing of several products such inks (it determines the appearance and gloss of paint; the reflectivity of highway paint), cement (it fixes upon hydration rate & strength of cement properties), pharmaceuticals, food (it decides the flavor of cocoa powder), make-up (it determines the appearances of cosmetics). Particle size is thus a key factor in several - and more and more increasing - industrial sector and development/manufacturing proceedings such as crushing, homogenization, emulsification, micro-fluidization when lab measurements are needed to track changes in particle size. This is particularly true for the pharmaceutical industry, where the size of active ingredients influences critical characteristics such as content uniformity, dissolution and absorption rates. Here, the so-called nano-biotechnology is key for competing onto the market: the convergence of nanotechnology and biotechnology, and in particular its applications in the medical sector are considered as one of the most promising and most advanced areas of nanotechnology in the EU and beyond. In fact, commercialisation efforts in nano-medicine are picking up worldwide. Over the past two decades scientists have learned to design, manufacture and manipulate nanoscale materials. At the point where nano-materials meet with a molecular understanding of cell function and disease development, nano-medicine emerges. Using nano-materials allows to target cancerous tissue, to transport drugs and imaging agents into cells or to stimulate cell responses supporting the healing process. For these applications nano-materials are unique as their scale corresponds to the scale of biomolecules and it is intuitively understandable that nano-materials could potentially be of great value for medical applications. The Global Nanotechnology Market is poised to grow at a CAGR of around 18.1% over the next decade to reach approximately $173.95 billion by 2025 and this represents a huge opportunity for the EU to boost the competitiveness of both large and SMEs in the sector, with large positive impact on the EU economy.
Classizer™ project can make the difference by introducing something new to Europe and beyond in terms of technology applied to particle size. Our solution can effectively meet the end-users/customers needs for accurate, real-time information for particle size bringing maximizing the costs and offering reliable and trusted information. As resulted from the market analysis (Section 2), this aspect becomes crucial in any growing market, EU included. We will take advantage of EU present needs building on the fact that present technologies for particle size, in particular addressed to complex fluid, suffer from data measurement incoherences, so our superior class device paired with a novel technology will represent the right solution at the right time for the industry
Our final scope is to introduce Classizer™ into the market our SPES. This will pass through the following strategic/operational business objectives:
1. To optimise our particle size analyser for introduction onto the Market
2. Set up partnerships with industrial partners, stakeholders, improving market research outcomes
3. Set up pilot actions to test our device in at least 3 different countries (already identified), with micro-targeted users
4. Achieve standards compliance; implement a sound IPR strategy basing on the results achieved during the pilots
5. Establish the full value chain, sales strategy, reducing time-to-first sell
Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far
During the past 6 months we carried out a Feasibility Study with the aim to validate technical, operation as well as economic viability.
The activities carried out to assess the project concentrated on developing Classizer™ evolutive prototype and the value chain to seed the phase of sale agreements with partners involved so fare, so bringing to pilot commercialisation.
1. The Technical and operational Feasibility:
we directly involved Mario Negri Institute for Pharmacological Research (MNI), SIPCAM, a marketing, R&D and marketing company, Lab. Pharmaceutical Technology and Law (PT&L) of Pharmaceutical Chemistry and Technology Department of the University of Pavia (Italy), the Urological Research Institute (URI) at the Hospital San Raffaele, the leading European urologic centre. They were involved in order to have a good representation of our end users. Activities dealt with checking the feasibility of Classizer™'s matching with their needs and expectations, with a core focus in smooth adaptivity of our solution. Then we proceeded with the production design to increase the prototype usability improve measurements reliability intra and inter-laboratory, and beta testing. To this purpose, 4 devices were manufactured and delivered to the beta-tester, enabling us to determine use and maintenance costs. The results then allowed us to proceed with a detailed product development plan, supported by the "Agile development methodology", using PRiSM session (Projects integrating Sustainable Methods). We then elaborate a plan for meeting the main relevant regulatory requirements necessary for the market entry in terms of key-steps, costs, timing, paired with a sound risk assessment and contingency plan.
In details, we involved 4 relevant national and international organisations representing our potential end-users with the aim to test Classizer™ for 1. increasing its usability, 2. improving measurements reliability intra and inter-laboratory, and for determining use and maintenance costs by the results of the device in use.
- Mario Negri Institute: EOS team has trained two Mario Negri Institute researchers on September 2017 on SPES technology and how use CLASSIZER ONE™ v0.7 device. A beta CLASSIZER ONE™ v0.7 unit has been assembled by EOS and provided to Mario Negri Institute 2th October 2017. The device has been installed at Environment Health Sciences department under the supervision of Dr. Diego Baderna (MNI) and its use is shared with the Molecular Biochemistry and Pharmacology departments held by Dr. Mario Salmona (MNI). EOS provided to MNI two different dielectric samples to conduct a periodically repeated inter-laboratory inter-operator validation. The first sample consist in a heterogeneous mix of mono-dispersed polystyrene spheres with diameters ranging from 200nm to few microns.
- SIPCAM is a marketing, R&D and marketing company for phytosanitary products, nutritional products and micro-granulated fertilisers with leadership vocation that: a) applies innovative agricultural research and development solutions, b)offers a wide portfolio of products for the main crops and c(invests in safe products for the farmer, the consumer and the Environment. EOS subscribed an agreement with SIPCAM for the validation of the SPES technology and beta-testing CLASSIZER ONE™ v0.7 device on agrochemicals products. Micro and nanoparticle characterisation is a crucial activity for both R&D and Quality Control of agrochemicals. Most of these products are based on heterogeneous mix of powders and materials. An accurate characterisation of formulations and product stability (e.g. to avoid aggregation) is needed. In the second half of 2017 EOS has validate the technology at his lab on samples provided by SIPCAM.
- Lab. Pharmaceutical Technology and Law (PT&L) of Pharmaceutical Chemistry and Technology Department of the University of Pavia (Italy) is a recognised scientific institute dedicated to formulation, characterisation and study of micro- and nano-particulate made of biodegradable and biocompatible polymers for drug delivery systems. As part of the validation and valorisation of its technological solutions, EOS made fully available its CLASSIZER ONE™ v0.7 at EOS labs to researchers of PT&L.
- The Urological Research Institute (URI) at the Hospital San Raffaele is the leading European urologic centre and holds unique opportunities to within one single unit address and investigate a variety of aspects of urogenital disorders (epidemiological, genetic, molecular, cellular, physiological, pharmacological, clinical) of immediate relevance for the individual patient as well as health-care system of the community. EOS has subscribed a partnership with Hospital San Raffaele to carry out a 30 months preclinical trial (i.e. fishing expedition). The aim is an extensive validation of the SPES technology for an enabling effective characterisation of the particulate in biological fluids such as urine. As part of the agreement, EOS has assembled and installed a CLASSIZER ONE™ v0.7 unit to URI and it will collaborate with URI in the data analysis. Research activities are under the supervision of Dr. Massimo Alfano (URI) and Prof. Andrea Salonia (URI).
Results achieved:
1. AVERAGE PARTICLE DIAMETER FROM PARTICLE SIZE DISTRIBUTION: CLASSIZER™ ONE v0.7 is able to discriminate the presence of several mono-disperse particle population in the heterogeneous mix provided. Good accuracy and better precision is retrieved by the instruments at the state of art.
2. PARTICLE SIZE DISTRIBUTION PEAK VALUE: The peak value of the particle size distribution is a sample parameter commonly considered by users, especially by Dynamic Light Scattering users.
3. SINGLE PARTICLE AVERAGE REFRACTIVE INDEX: The capability of SPES and CLASSIZER™ ONE v0.7 to measure the average refractive index of single measured particles is one of the most valuable added value of the EOS solution for particle analysis.
4. NUMERICAL PARTICLE CONCENTRATION: The numerical concentration (i.e. number of particles per volume) is one of the most important parameter for quality control of pharmaceuticals (e.g. measuring the concentration of large impurities in an injectable pharmaceutical products).
The Economic Viability started with a realistic bottom-up approach in which the number of reachable customers were estimated according to in progress and existing contacts and potential quick leads. This implied the need to further map the target markets and related go-to-market strategy. The technical feasibility also fed the final product production cost and price. A cash-flow, break-even analysis was also conducted.
This resulted in a clear understanding of the market scenario and conditions, potentials, competitive landscape, target users segmentation, allowing us to clearly design our go-to-market strategy, including budget and forecast analysis.
The activities carried out to assess the project concentrated on developing Classizer™ evolutive prototype and the value chain to seed the phase of sale agreements with partners involved so fare, so bringing to pilot commercialisation.
1. The Technical and operational Feasibility:
we directly involved Mario Negri Institute for Pharmacological Research (MNI), SIPCAM, a marketing, R&D and marketing company, Lab. Pharmaceutical Technology and Law (PT&L) of Pharmaceutical Chemistry and Technology Department of the University of Pavia (Italy), the Urological Research Institute (URI) at the Hospital San Raffaele, the leading European urologic centre. They were involved in order to have a good representation of our end users. Activities dealt with checking the feasibility of Classizer™'s matching with their needs and expectations, with a core focus in smooth adaptivity of our solution. Then we proceeded with the production design to increase the prototype usability improve measurements reliability intra and inter-laboratory, and beta testing. To this purpose, 4 devices were manufactured and delivered to the beta-tester, enabling us to determine use and maintenance costs. The results then allowed us to proceed with a detailed product development plan, supported by the "Agile development methodology", using PRiSM session (Projects integrating Sustainable Methods). We then elaborate a plan for meeting the main relevant regulatory requirements necessary for the market entry in terms of key-steps, costs, timing, paired with a sound risk assessment and contingency plan.
In details, we involved 4 relevant national and international organisations representing our potential end-users with the aim to test Classizer™ for 1. increasing its usability, 2. improving measurements reliability intra and inter-laboratory, and for determining use and maintenance costs by the results of the device in use.
- Mario Negri Institute: EOS team has trained two Mario Negri Institute researchers on September 2017 on SPES technology and how use CLASSIZER ONE™ v0.7 device. A beta CLASSIZER ONE™ v0.7 unit has been assembled by EOS and provided to Mario Negri Institute 2th October 2017. The device has been installed at Environment Health Sciences department under the supervision of Dr. Diego Baderna (MNI) and its use is shared with the Molecular Biochemistry and Pharmacology departments held by Dr. Mario Salmona (MNI). EOS provided to MNI two different dielectric samples to conduct a periodically repeated inter-laboratory inter-operator validation. The first sample consist in a heterogeneous mix of mono-dispersed polystyrene spheres with diameters ranging from 200nm to few microns.
- SIPCAM is a marketing, R&D and marketing company for phytosanitary products, nutritional products and micro-granulated fertilisers with leadership vocation that: a) applies innovative agricultural research and development solutions, b)offers a wide portfolio of products for the main crops and c(invests in safe products for the farmer, the consumer and the Environment. EOS subscribed an agreement with SIPCAM for the validation of the SPES technology and beta-testing CLASSIZER ONE™ v0.7 device on agrochemicals products. Micro and nanoparticle characterisation is a crucial activity for both R&D and Quality Control of agrochemicals. Most of these products are based on heterogeneous mix of powders and materials. An accurate characterisation of formulations and product stability (e.g. to avoid aggregation) is needed. In the second half of 2017 EOS has validate the technology at his lab on samples provided by SIPCAM.
- Lab. Pharmaceutical Technology and Law (PT&L) of Pharmaceutical Chemistry and Technology Department of the University of Pavia (Italy) is a recognised scientific institute dedicated to formulation, characterisation and study of micro- and nano-particulate made of biodegradable and biocompatible polymers for drug delivery systems. As part of the validation and valorisation of its technological solutions, EOS made fully available its CLASSIZER ONE™ v0.7 at EOS labs to researchers of PT&L.
- The Urological Research Institute (URI) at the Hospital San Raffaele is the leading European urologic centre and holds unique opportunities to within one single unit address and investigate a variety of aspects of urogenital disorders (epidemiological, genetic, molecular, cellular, physiological, pharmacological, clinical) of immediate relevance for the individual patient as well as health-care system of the community. EOS has subscribed a partnership with Hospital San Raffaele to carry out a 30 months preclinical trial (i.e. fishing expedition). The aim is an extensive validation of the SPES technology for an enabling effective characterisation of the particulate in biological fluids such as urine. As part of the agreement, EOS has assembled and installed a CLASSIZER ONE™ v0.7 unit to URI and it will collaborate with URI in the data analysis. Research activities are under the supervision of Dr. Massimo Alfano (URI) and Prof. Andrea Salonia (URI).
Results achieved:
1. AVERAGE PARTICLE DIAMETER FROM PARTICLE SIZE DISTRIBUTION: CLASSIZER™ ONE v0.7 is able to discriminate the presence of several mono-disperse particle population in the heterogeneous mix provided. Good accuracy and better precision is retrieved by the instruments at the state of art.
2. PARTICLE SIZE DISTRIBUTION PEAK VALUE: The peak value of the particle size distribution is a sample parameter commonly considered by users, especially by Dynamic Light Scattering users.
3. SINGLE PARTICLE AVERAGE REFRACTIVE INDEX: The capability of SPES and CLASSIZER™ ONE v0.7 to measure the average refractive index of single measured particles is one of the most valuable added value of the EOS solution for particle analysis.
4. NUMERICAL PARTICLE CONCENTRATION: The numerical concentration (i.e. number of particles per volume) is one of the most important parameter for quality control of pharmaceuticals (e.g. measuring the concentration of large impurities in an injectable pharmaceutical products).
The Economic Viability started with a realistic bottom-up approach in which the number of reachable customers were estimated according to in progress and existing contacts and potential quick leads. This implied the need to further map the target markets and related go-to-market strategy. The technical feasibility also fed the final product production cost and price. A cash-flow, break-even analysis was also conducted.
This resulted in a clear understanding of the market scenario and conditions, potentials, competitive landscape, target users segmentation, allowing us to clearly design our go-to-market strategy, including budget and forecast analysis.
Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)
The Feasibility assessment and the results achieved during the recent 6 months activities definitively confirmed both the economic, technical, operational viability of our proposed innovation. It was furthermore key to understand in details the growth potential of EOS as a company and our value proposition: Classizer™, in fact, addresses composition certification and will be used by customers who are producing their own liquids/materials, to certify their won production adequately. As today, EOS activity is 90% of the first and 10% of the second, however the results from the Feasibility Study and the discussion with our key partners, stakeholders and beta-testers were so relevant to somehow pivot our value proposition: in five years time EOS
company expects an inversion of activities to 10% of the first and 90% of the second, due to the
increase in market position for Classizer™. In fact, we understood that Classizer™’s proposition, in a general sense can be as a solution provider, in particular within the “industrial online measurement” market to control and carry out data analysis in material preparation processes in real time. This means for EOS to move from a merely generic “solution provider” to a “Technology Transfer Service Provider” and “cloud-based/IoT-based services”, with the view of increase GMP compliance, increase the efficiency of customers production processes.
On a business level, the market research analysis confirmed the assumptions for us to addressed the identified countries as the most promising ones, resulting in a full understanding of the market conditions, competitive landscape, potential growth and trends to consider for further development and for taking advantage of the opportunities in the Particle Sizing Analysis market sector. We confirm our development path in the framework of extended and increasing demand of particle size analysis in the industry sector in the upcoming years, which promises significant improvements in the pace, productivity, predictability and profitability of our collective efforts.
Basing on the data we collected during the 6 months so far, we were also able to perfectly shape our customer base and to better understand the needs and demands of our value chain as well. This had a major impact on our capacity to re-design and fine-tune our Classizer™ evolutive prototype, tailored on the potential users needs and demands and to include added valuable features to their benefit. This was also paired with a review of our policy price, defined according to the type of end-users, representing a concrete milestone in the wide expansion plan in the medium-long term.
All the data and information gathered from the technical side of the feasibility study were instrumental to validate our Classizer™ performances in use, which are crucial to meet the market demands. The feedback collected from our beta-testers do contribute to find tune our product design, understanding in details potential customers’ preferred features and performances in use, as well as to fine-tune our innovative approach, methodology as well business model. This of course revealed key to carefully screen the best final product to be commercialised on the market, assessing and validating our Minimum Viable Product (MVP). The feedback collected from our industrial partners. stakeholders and third parties as well as our potential end-users/customers had a decisive role for us to better understand the demands and expectations also in terms of improvement over time of our pipeline products, in particular showing the need to revise mid-term targets at both technical and commercial levels.
As a final results, the project confirms its full viability, thus paving the way for the further operational and “demonstration” phase.
company expects an inversion of activities to 10% of the first and 90% of the second, due to the
increase in market position for Classizer™. In fact, we understood that Classizer™’s proposition, in a general sense can be as a solution provider, in particular within the “industrial online measurement” market to control and carry out data analysis in material preparation processes in real time. This means for EOS to move from a merely generic “solution provider” to a “Technology Transfer Service Provider” and “cloud-based/IoT-based services”, with the view of increase GMP compliance, increase the efficiency of customers production processes.
On a business level, the market research analysis confirmed the assumptions for us to addressed the identified countries as the most promising ones, resulting in a full understanding of the market conditions, competitive landscape, potential growth and trends to consider for further development and for taking advantage of the opportunities in the Particle Sizing Analysis market sector. We confirm our development path in the framework of extended and increasing demand of particle size analysis in the industry sector in the upcoming years, which promises significant improvements in the pace, productivity, predictability and profitability of our collective efforts.
Basing on the data we collected during the 6 months so far, we were also able to perfectly shape our customer base and to better understand the needs and demands of our value chain as well. This had a major impact on our capacity to re-design and fine-tune our Classizer™ evolutive prototype, tailored on the potential users needs and demands and to include added valuable features to their benefit. This was also paired with a review of our policy price, defined according to the type of end-users, representing a concrete milestone in the wide expansion plan in the medium-long term.
All the data and information gathered from the technical side of the feasibility study were instrumental to validate our Classizer™ performances in use, which are crucial to meet the market demands. The feedback collected from our beta-testers do contribute to find tune our product design, understanding in details potential customers’ preferred features and performances in use, as well as to fine-tune our innovative approach, methodology as well business model. This of course revealed key to carefully screen the best final product to be commercialised on the market, assessing and validating our Minimum Viable Product (MVP). The feedback collected from our industrial partners. stakeholders and third parties as well as our potential end-users/customers had a decisive role for us to better understand the demands and expectations also in terms of improvement over time of our pipeline products, in particular showing the need to revise mid-term targets at both technical and commercial levels.
As a final results, the project confirms its full viability, thus paving the way for the further operational and “demonstration” phase.