[ BUSINESS SOLUTION ]

1

WORKING WITH WATERS Chiesi’s focus on entrepreneurial collaboration also serves as the basis of the 10 year relationship between its researchers and Waters.

Dr. Lewis describes the importance of working with the right partners: “We need to find the right people who have the right mindset and understand what we want to do. Waters is easy to work with. It’s about the people and what they can offer.”

That mindset includes a focus on the specific needs of drug discovery researchers, something Dr. Lewis values greatly. He explains: “Waters works hard to ensure its instrumentation is suitable for the pharmaceutical industry. It’s a lot of work to achieve software that does what we need it to do. Waters provides the tools that we need to do our jobs – and they enable us to do our jobs well.”

Technology: ACQUITY UPLC, ACQUITY QDa, Empower Software, and the Nugenesis Lab Management System

PHARMACEUTICAL R&D AT THE CHIESI GROUPThe mission of the Chiesi Group has remained the same for more than 80 years – produce innovative pharmaceutical solutions to improve the quality of human life. One of today’s top 50 pharmaceutical companies worldwide, Chiesi’s success is based on the company’s continuous emphasis on the entrepreneurial spirit.

The Chiesi Group focuses on the research, development, production and commercialization of innovative medicines in the respiratory, neonatology, rare disease, and special care therapeutic areas. From its original location in Parma, Italy, the Chiesi Group now has a presence in 26 countries and exports to more than 70 countries. The company employs approximately 4,813 people – 671 of whom are dedicated to R&D activities and 700 of whom work at production sites in Italy, France, and Brazil.

In 2009 Dr. David Lewis founded the company’s Chippenham, UK office and tasked the researchers there to continue to develop products at the cutting edge of aerosol science, with a focus on pressurized systems. Chiesi Chippenham has invested heavily in multiple disciplines related to drug discovery.

He explains: “Our objective is to ensure we know as much as we can about inhalation drug delivery. We need to be 5–10 years ahead, so a product could be launched on the market in 5–10 years. That means we need to be 20–30 years ahead in the research to make that happen.”

Future-Proofing Pharmaceutical R&D to Accelerate Aerosol Science Innovation

Waters UPLC systems with the ACQUITY QDa Mass Detector and informatics solutions enable pharmaceutical R&D teams to stay at the cutting edge of aerosol and inhalation drug delivery research at the Chiesi Group’s Chippenham laboratory in the United Kingdom

Make sure there are no widows in the text

The Chiesi Group.

Dr. David Lewis, Director of Aerosol Research at The Chiesi Group, Chippenham, UK.

[ BUSINESS SOLUTION ]

2Future-Proofing Pharmaceutical R&D to Accelerate Aerosol Science Innovation

Dr. Lewis is co-inventor of 29 patents relating to pressurized metered dose inhaler formulations and devices. These inventions resulted in the Chiesi Modulite technology, which led to formulations of beclomethasone dipropionate, budesonide, formoterol, and a beclomethasone dipropionate-formoterol combination becoming commercialized in several European countries.

The Chiesi Group also actively promotes not only the generation of scientific evidence, but also the dissemination of knowledge among the scientific community, the public and academic institutions. As such, Chiesi Chippenham sponsors research at universities worldwide, including Kings College London, Loughborough University, Bristol University (UK), University of Alberta (Canada), Monash University, and Sydney University (Australia). That support includes funding as well as access to Chiesi’s laboratories and instrumentation.

The strong relationship building and collaboration efforts by Dr. Lewis and his team has enabled Chiesi Chippenham to strengthen its leadership position on the cutting edge of inhalation drug delivery research.

BREAKING BOUNDARIES IN DRUG DISCOVERY RESEARCH

In 2014, Chiesi Chippenham invested in Waters™ ACQUITY™ UPLC,™ with PDA and ACQUITY QDa,™ and informatics software, with the aim of reducing analytical bottlenecks in their workflow. The Chippenham team identified that it spent more than 9 hours on its Process Analytical Technology (PAT), the majority on sample analysis, where sample run time was more than six hours. For a lean team, this bottleneck impacted their working process in Chippenham. By investing in improved hardware and developing a simplified workflow, Chiesi managed to reduce analysis run time to under one hour.

The investment in software also reduced the majority of paperwork by automating processes and gave the small innovation team at Chippenham more ease of management including automated approvals.

The results comprised faster assay run time, higher sensitivity and high-speed assay development through automation. This meant fewer delays, efficient workflow and reduced paperwork, contributing a significant time saving of seven hours per day.

Dr. Lewis continues: “We needed to future–proof the science as much as possible. We don’t want anything that’s not going to be supported later. Our laboratory instrumentation and software applications need to be compatible today and tomorrow as well. This is important due to regulatory requirements changing over time. Waters offers that.”

Chiesi Chippenham views the ACQUITY QDa Mass Detector as a step in their continuous plan to expand – and challenge – their findings in drug discovery research. The goal is to broaden the laboratory’s technological capabilities and find new innovations in inhalation drug delivery.

Chiesi Chippenham was looking for an instrument that both complemented and enhanced the team’s research. Dr. Lewis adds: “If I ’m getting a value out of an instrument, what does it tell me? If we interact with many different instruments, we get a bigger picture to make better-informed decisions.”

Chiesi’s entrepreneurial culture means the company is always evaluating new technology to see how it can improve current and future pharmaceutical product pipelines. Dr. Lewis saw the potential of using cutting-edge Waters UPLC hardware and chemistry with the ACQUITY QDa Mass Detector to give the Chiesi Group a competitive advantage in the time-sensitive pharmaceutical industry.

“The ACQUITY QDa coupled with an

ACQUITY UPLC system is keeping us

in touch with the future. It helps reduce

analysis time and increase productivity. The

ACQUITY QDa is easy to use, requiring less

user expertise. We’ve found it very useful.”

DR. DAVID LEWISChiesi Chippenham’s Director of Aerosol Research

ACQUITY UPLC with ACQUITY QDa, Chiesi, Chippenham, UK.

[ BUSINESS SOLUTION ]

3Future-Proofing Pharmaceutical R&D to Accelerate Aerosol Science Innovation 3

Those improvements help Chiesi scientists stay focused on pushing the boundaries of drug discovery.

Another one of its appealing features is the ACQUITY QDa’s integration with Waters chromatography systems and optical detectors, as well as Waters scientific software products. That compatibility helps Chiesi streamline and simplify by combining mass spectral information seamlessly into the same workflow.

The ACQUITY QDa Mass Detector gives more selectivity than optical detection alone, and therefore gives more confidence in the results.

DATA = THE BACKBONE OF PHARMACEUTICAL RESEARCHIn addition to the Waters instrumentation, Waters Laboratory Informatics Software, Empower™ Software and NuGenesis™ Lab Management System, provides Chiesi Chippenham with a powerful suite of software solutions for instrument control, scientific data management, scientific search, network integration, and compliance management to streamline their analytical laboratory operations.

That investment has resulted in significant benefits, particularly in terms of speed, automation, and advanced data tools. Faster laboratory workflows enable a higher level of data output – freeing up time for more important tasks. Automation prevents errors from manual data input and transcription, another time saver. Additionally, all information is saved as meta data with identical formats for document descriptors, improving data searchability.

Data is the backbone of pharmaceutical research, and Waters has established itself as a strong partner in Chiesi Chippenham’s quest to gather and analyze as much as possible. Dr. Lewis comments: “The more data I have, the better picture I have. And the more samples I can process, the more data I have. Our fastest cycle time is around one minute. This high turnover of samples, linking to the data systems, helps us to build a much richer picture.”

Dr. Lewis explains how vital Waters’ support is to Chiesi’s long-term vision: “We don’t want a company that will disappear. Waters wants compatibility between instrumentation and scientific software as we do. We needed a database-driven system. Waters did that years ago. You don’t see that consistency from other companies because it ’s a lot of work.”

(In 1992, Waters introduced the first chromatography software that was built on a relational database. They did this because they understood how important it was for companies to be able to track results to meet ever increasing regulatory challenges.)

The Chippenham team relies on the Waters Empower Software and NuGenesis Lab Management System, which combines synergistic data, workflow, and sample management capabilities to support the entire product lifecycle from discovery through manufacturing. The integrated electronic workflow, helps maintain the integrity of the data.

ACQUITY QDa DETECTOR The ACQUITY QDa Detector complements optical detection, such as the PDA Detector, by confirming the identity of compounds with mass spectral information. Additionally, the ACQUITY QDa Mass Detector extends the limits of sample detection for a chromatographic separation by quantifying compounds having no UV response or that are present at levels not detectable and quantifiable by optical detection. By simplifying laboratory workflows, the detector enhances the value of every analysis and increases productivity by eliminating the need to run additional assays or turn to time-consuming alternative techniques to establish with certainty the levels and identity of specific sample compounds. This has increased sample throughput, providing substantial time and cost saving benefits.

The ACQUITY QDa Mass Detector, Chiesi, Chippenham, UK.

[ BUSINESS SOLUTION ]

4Future-Proofing Pharmaceutical R&D to Accelerate Aerosol Science Innovation

The capabilities provided by NuGenesis help Chiesi Chippenham’s researchers enable software integration and standardization without the complex, costly and time–consuming deployments often encountered with traditional information management solutions. That’s valuable because companies want to avoid large disruptions to their data-integration systems and the related costs, additional infrastructure, inevitable disruptions to workflows and logistical issues.

NuGenesis also helps the Chiesi Group reduce costs, accelerate decision making, improve laboratory effectiveness, and get their products to market faster. Building a paperless laboratory from the ground up enabled Chiesi to avoid paper costs, build in all lab approvals with 21-CFR compliant e-signatures, and streamline all bottlenecks. Automation provided by the software reduces the likelihood of transcription mistakes and decreases time checking data. Dr. Lewis explains: “We need to process, interpret, visualize, and compare the most complex data, and then turn it into meaningful information quickly and simply.”

MAINTAINING CONSISTENCY ACROSS R&D LOCATIONS

Because the Chiesi Chippenham office works closely with its other R&D locations, maintaining consistency is an important part of their investment in Waters technology, both in their laboratory and across other R&D locations. By breaking up silos of information to encourage collaboration with other scientists, locations and external partners, the Chiesi Group can extend the value of their research data and speed up the innovation process.

In addition to the Chiesi Chippenham site, Chiesi’s R&D centers are located in Parma; Paris, France; Cary, NC, USA; and Oxford, United Kingdom. These locations integrate their efforts to advance Chiesi’s pre-clinical, clinical, and registration programs. Chiesi Chippenham also works closely with academic collaborators, supporting their research and gaining insight that can lead to scientific breakthroughs.

In addition to the company’s internal scientists, Chiesi works closely with academic researchers, giving them both funding and access to Waters instrumentation in the Chippenham laboratory to complete their research. These relationships are a key part of Chiesi’s ability to discover new innovations in aerosol science. And that innovation is the overall goal of Chiesi Chippenham.

Replicating the same instrumentation and methods across sites improves the ability of different Chiesi locations to easily share data and information, work and collaborate more efficiently, and transfer methods using Waters chemistries and people between sites. For example, Chiesi’s Parma location has also invested in the Waters ACQUITY QDa and ACQUITY UPLC systems – which will make future research collaborations between the two locations faster and easier.

“We need to continually adapt in this

industry. We need to be in an area where

everyone else thinks what we’re doing is

impossible. We’re looking at the edge of

the curve.”

DR. DAVID LEWISChiesi Chippenham’s Director of Aerosol Research

“We don’t want a company that will

disappear. Waters wants compatibility

between instrumentation and scientific

software as we do. We needed a

database-driven system. Waters did that

years ago. You don’t see that consistency

from other companies because it’s a lot

of work.”

DR. DAVID LEWISChiesi Chippenham’s Director of Aerosol Research

The laboratory at Chiesi, Chippenham, UK.

[ BUSINESS SOLUTION ]

5Future-Proofing Pharmaceutical R&D to Accelerate Aerosol Science Innovation

The Chiesi Group has found using the same instrumentation and column chemistries across laboratory sites has many benefits, including easy method transfers, significant time savings and simplified decision making. Without this consistency of instruments across sites, it would be more challenging and time-consuming to transfer methods and information. The Parma Quality Control lab recently used the ACQUITY QDa in combination with ACQUITY UPLC H–Class System to streamline five methods down to just one assay, saving substantial time, as well as reducing sample prep time and enabling faster batch release, reducing release from 2 days to ten minutes. Chiesi scientists have also actively worked to get the time required for samples analysis down to just one minute.

The combination of the ACQUITY UPLC, ACQUITY QDa, chemistries, and informatics (Empower and NuGenesis) streamlines basic method development for companies like Chiesi, which in turn enables the completion of entire feasibility studies in significantly reduced time.

RESULTS

The relationship between Cheisi and Waters has enabled Dr. Lewis and his team to continue to push the boundaries of the drug discovery research process. Quality instrumentation and software from Waters has allowed the Cheisi Chippenham scientists to maximize the applicability of their research – and the innovations that result from it. It’s a partnership that’s improved their ability to work closely with other researchers and laboratories, as is the collaborative corporate culture of the Chiesi Group, whether that’s between company locations or with academic research partners.

It’s an alliance that helps Chiesi Chippenham stay on the cutting edge of its field.

Dr. Lewis explains: “You always need new instrumentation, new concepts, new ideas. We’re here to research and problem solve as much as we can. If you do not keep ahead of this thinking, someone else will.”

Dr. Lewis believes the high levels of collaboration between pharmaceutical researchers, instrumentation companies and academics are the foundation of his team’s success. And that’s true whether the research results are successful – or not. It also helps Chiesi scientists to decide which projects are promising enough to pursue, or alternatively, which ones may be better not to pursue.

He explains: “You may get down a long road, and your research is a dead end. Yet that research is extremely important. Some of that research doesn’t get published. But it’s very useful to create discussions. We’re trying to push ourselves in a direction that we haven’t understood or found before. We collaborate with other researchers around the world, and that helps us step over the line into something people don’t believe exists.”

Success in drug discovery requires seeing both the bigger picture and the long–term possibilities. The research data the Chippenham team gathers holds great value for the company, and it’s important to invest in resources today that will make it easier to use that data in other ways in the future – because it has implications not only for today, but also tomorrow, next year, and many years from now.

Dr. Lewis explains: “We need to process, interpret, visualize and compare the most complex data, and turn it into meaningful information quickly and simply. It’s to do with scalability and the ability to stay productive.”

SUMMARY

It ’s becoming more important for pharmaceutical companies like the Chiesi Group to integrate forward-looking strategies to achieve excellence and use their growing knowledge to make decisions quickly.

Leveraging research data helps the Chiesi Group to identify new technology and new potential drug candidates faster, which in turn helps the company develop them into products that can be introduced on the market more quickly. It also provides support for regulatory compliance and product quality control.

“If you’re trying to advance and be

progressive, you need to build on what you

did last year. Our investment into Waters in

the laboratory enables us to do this.”

DR. DAVID LEWISChiesi Chippenham’s Director of Aerosol Research

Five QC methods for batch release were replaced using ACQUITY UPLC H-Class/ ACQUITY QDa/ ACQUITY Evaporative Light Scattering Detector (ELSD).

Waters, The Science of What’s Possible, ACQUITY, UPLC, QDa, NuGenesis, and Empower are trademarks of Waters Corporation. All other trademarks are the property of their respective owners.

©2018 Waters Corporation. Produced in the U.S.A. July 2018 720006294EN PM-PDF

[ BUSINESS SOLUTION ]

Waters Corporation 34 Maple Street Milford, MA 01757 U.S.A. T: 1 508 478 2000 F: 1 508 872 1990 www.waters.com

Dr. Lewis explains: “My opinion is large pharma companies can’t be complacent because there are small companies that are quite happy to be clever. New data and improved analytical techniques will enhance the opportunity for innovation and strengthen the drug-development process .”

“In pharmaceutical research it ’s important to continually build new ideas and work with new technology. We don’t ever want to get the point where we think we know it all or understand it all.”

“We always need to challenge what we’re doing in terms of how to do drug delivery, instrumentation, interpretation, data processing methods or combinations thereof.”

Its partnership with Waters will help the Chiesi Group continue to develop more efficient workflows in drug development and QC. And that, Dr. Lewis believes, will serve as the basis for the company’s growing success.

Special thanks to Chiesi Parma for its contributions to this case study.

“Collaboration is key because there’s

too much to understand. The

pharmaceutical industry needs to stay

ahead of the game if they’re going to

deliver tomorrow’s medicines.”

DR. DAVID LEWISChiesi Chippenham’s Director of Aerosol Research

Waters instruments at the Chiesi laboratory, Chippenham, UK.

The Chiesi Group.