The Importance of a Global Leader in Small Molecule Manufacturing During the COVID-19 Pandemic

The Importance of a Global Leader in Small Molecule Manufacturing During the COVID-19 Pandemic

Dec 09, 2020PAP-Q4-20-CL-025

Seqens was formed in December 2018 when Novacap merged with PCI Synthesis, PCAS, Uetikon, and Proteus. With 24 manufacturing plants and three R&D centers in Europe, North America, and Asia, we are an integrated global leader in pharmaceutical synthesis and specialty ingredients. During the COVID-19 pandemic, we have used our expertise in small molecule process development and scale-up to provide optimal routes to potential therapeutics and to reshore key compounds in short supply, as well as to produce isopropanol-based hand sanitizers for our local communities. Going forward, we will continue to invest in innovation to expand our onshoring efforts and increase our ability to produce the complex, next-generation molecules, including highly potent molecules, that will remain in demand for the foreseeable future.

Relocation to Address Shortages of Key Molecules

Even before the COVID-19 pandemic, the pharmaceutical industry was faced with a shortage of several important small molecule drug substances and drug products. The emergence of the pandemic highlighted this issue, particular for those molecules for which most manufacturing capacity has been located in Asia, especially China and India. 

These shortages occurred for several reasons. In some cases, there were production issues, including those related to quality. In others, it was simply a capacity issue. Supply chain issues were also at play. These problems were further magnified by the shutdowns and limited operations of many facilities in Asia during the pandemic. 

Our focus at Seqens has been to identify the small molecules that are in shortage and relocate production to the West. Relocation in this sense does not require building new plants. Our facilities, like many other contract development and manufacturing organizations (CDMOs) and pharmaceutical companies, are multipurpose and able to produce many different types of molecules. Modernization and expansion of capacity are needed to produce molecules in short supply. 

The first step in this endeavor is to reevaluate the production processes and identify ways to improve the synthesis routes by leveraging newer, more efficient technologies that have been introduced since these molecules were first produced in India and China over the last two decades. Innovative approaches are ideally more cost-effective, environmentally friendly, and provide higher-quality products. Innovation is thus fundamental to successful reshoring.

Benefits of Supply Chain Integration

Even before the shortcomings of global supply chains became apparent in the context of the pandemic, Seqens was committed to providing an integrated, end-to-end supply chain for its clients. Seqens is capable of performing all necessary steps under one roof, from early intermediates in the early development process through commercial manufacturing, freeing our clients from having to manage inventory and logistics. While sourcing concerns appear more challenging than ever, Seqens’ integrated supply chain has remained resilient, providing a simple, comprehensive solution to accelerate project timelines.

Digitalization Aids Reshoring Activities

One of the necessary areas of innovation for many parts of the value chain that wish to reshore pharmaceutical production is digitalization. For Seqens, digitalization can improve both the efficiency of research and development and the economics of commercial processes. Data mining can help identify older molecules that can be used for new applications, such as for synthethic routes.

Digitalization at Seqens enables us to accelerate our improvement and innovation processes, but also to reach new objectives thanks to the technologies we have implemented. The implementation of a wide range of digitalization tools and solutions has enabled the group to accelerate R&D, constantly improve production quality, guarantee operator safety, and ultimately ensure the satisfaction of our customers. 

Our digital solutions range from automated mining equipment for the extraction of sodium bicarbonate to the use of digital platforms in our production facilities that enable better coordination production and maintenance scheduling and forecasting, quality assurance, and EH&S activities, as well as interactions with external partners. The Seqens Digiqual document and quality process management solution has been implemented at all production sites, ensuring a harmonization of practices while still allowing for customization to meet the unique needs at each location. We also invested in state-of-the-art analytical tools to optimize the efficiency of our analytical labs, including remote control of experiments. 

Even before the shortcomings of global supply chains became apparent in the context of the pandemic, Seqens was committed to providing an integrated, end-to-end supply chain for its clients.

Visualization of the supply chain has also been improved with the use of digital solutions. Seqens’ QlikView solution provides a global, instantaneous, and exhaustive vision of activity across the supply chain, combined with a modeling capability to evaluate potential future needs. Users from the general manager to commercial operations through finance and supply chain members can readily obtain real-time data and assess the activity level of the company.

All of these efforts ultimately enable Seqens to better serve our customers. They are also supported by a new global customer relationship management platform (OneCRM) designed to strengthen the collaboration between our internal teams with the objective of improving the customer experience. These advances, which are gradually being rolled out to all Seqens sites around the world, are the first of many new solutions necessary for success of our recovery and relocation plan in France. Indeed, only an industrial tool that functions optimally through digitalization will enable a sustainable future for these investments. 

PA_Q420_Seqens_Sidebar

Investing in Highly Potent Capabilities

One of the primary trends in the pharmaceutical industry today is the increasing number of potent or highly potent APIs (HPAPIs) under development. Approximately 40–50% of molecules in the pipeline fall in this category and require highly specialized facilities and equipment and skilled and trained operators for their safe production. These molecules often require complex chemistry for their synthesis. The containment systems required to protect workers and the environment are also complex technologies. From an investment standpoint, these systems are also costly. As a result, capacity has often not kept up with demand.

Seqens has carefully evaluated the risk of expanding our capabilities in the HPAPI field and concluded there will be a long-term need for these services going forward. In late August, we inaugurated an innovative HPAPI unit at our Villeneuve-La-Garenne site. This investment of $35 million (€30 million) in one of the three leading technologies in pharmaceutical synthesis, demonstrates the Seqens Group’s ability to design, develop, and industrialize the most complex molecules while maintaining a high level of quality, safety, and respect for the environment. The construction of a second plant for HPAPIs in France is currently under consideration.

Novel Biocatalysts Enable Small Molecule Manufacturing

Our greatest expertise at Seqens lies in developing and producing highly complex molecules using a unique skill set and a very broad continuum of technologies that encompasses both chemo- and biocatalysis. We bring together experience in enzymatic technologies and pharmaceutical route development with the development of optimized enzymes for specific transformations.

We also develop proprietary biocatalyst solutions. The most recent offering, launched in December 2019 by our Protéus subsidiary, are our SEQENZYM® Enzyme Kits, which contain enzymes selected among our extensive library of extremophile strains for fast early screening of biocatalysts. The seven different easy-to-use enzyme kits can accelerate screening of enzymes for molecular synthesis transformations by facilitating rapid assessment and identification of biocatalysts that afford desired conversion rates, selectivities, operating conditions, and kinetics.

Award-Winning COVID-19 Support Efforts

During the COVID-19 pandemic, Seqens has been involved though partnerships with big pharma and biotech companies in the development of novel molecules with potential as COVID-19 therapeutics and more efficient routes to known compounds for repositioning, as well as the expansion of isopropanol production for the formulation of hand sanitizers. For the latter, we implemented the manufacture of hydroalcoholic and gel solutions for local communities at our plants in France, the UK, Canada and the United States in just a few months. 

Indeed, Seqens’ mobilization in response to COVID-19 has earned the company a 2020 European Responsible Care® Award for our project “Caring in Covid-19 Times.” The special awards, issued by the European pharmaceutical trade group CEFIC, were based on the rapid engagement of our teams and workshops to propose and implement solutions to accelerate the fight against COVID-19 while adapting production lines to the market and providing support to local communities, populations at risk, and those in need by donating hand sanitizer.

To aid in antiviral candidate development, Seqens screened thousands of compounds in clinical databases and chemical abstracts, identifying both new chemical entities and existing drug substances with the potential to treat COVID-19. A smaller set of more than 100 compounds — for which Seqens was in a position to improve and accelerate by simplifying and reducing the synthesis stages and using innovative proprietary solutions — was then selected with the goal of providing the most effective solutions with the fastest routes to market in the context of this severe crisis

Seqens participates in the INOVA COVID-19 platform, which coordinates the achievements of the global players fighting against the novel coronavirus. Our researchers are collaborating at all levels across numerous areas of expertise (organic synthesis, analytical sciences, process engineering, process safety, thermodynamic and kinetic modeling) to develop robust solutions.

Global Leader in Small Molecule Manufacturing 

Seqens has 24 plants worldwide, with a strong presence in Europe and in the United States. Our rapid growth will continue to be driven by ongoing investments in our plants. Despite the challenges experienced in 2020, we have additional investments planned in 2021 and 2022, and some announcements are forthcoming before the end of the year. In a nutshell, Seqens is on the path forward as a global key leader for small molecules.

Our dedication to this goal is reflected in the recent corporate social responsibility evaluations Seqens received from EcoVadis. Thirteen of our 24 operational entities have been assessed by EcoVadis, with five obtaining the Platinum level (top 1%), six the Gold level (top 5%), and two the Silver level.

Safe and Efficient Synthesis Using Flow Chemistry

Seqens has taken cues from other chemistry-based industries to leverage flow chemistry as part of an effort to make industrial processes safer. Continuous operation using flow chemistry approaches increase manufacturing efficiency by reducing reaction volumes, offering better control of reaction temperatures and exothermicity and a tighter residence time distribution than batch processes, and in many cases better selectivity. By minimizing secondary reactions and the formation of impurities, flow chemistry offers clear advantages in terms of quality while simultaneously reducing the environmental footprint. At the Seqens Lab in Porcheville, France, we systematically evaluate the feasibility of flow chemistry approaches for customer projects. Further investments in these capabilities are in the works, which by the end of 2020 will include a new GMP pilot plant designed for nitration-, diazotation-, or halogenation-type reactions and production of precommercial batches up to the ton scale. Bringing back activity in Europe to secure the supply chain will go also through this kind of safe and low environmental impact investments.

Prepared for Post-Pandemic Growth

Seqens will continue to invest in innovation to maintain our competitiveness and gain access to markets that require specialized expertise and capabilities. We will build on our existing strengths in small molecule synthesis, focusing on HPAPIs and other challenging compounds we can positively impact.

Simultaneously, we will continue to focus on molecules that are in short supply in most Western countries. As an integrated player in the drug production chain, from the production of intermediates to the production of active pharmaceutical ingredients and from research and development to industrialization, Seqens has the technical and industrial capacities to relocate and increase the production capacity of essential and critical molecules.

We are committed to developing a skilled workforce and have already doubled the number of work-study students and apprentices, particularly in technical fields. In 2021, more than 150 young people will be welcomed to our sites to learn our businesses. At least 10% of the group’s employees will continue to work on the development of new products and innovative processes. Our culture of performance, rigor, and continuous improvement enables us to provide quality products in compliance with the strictest quality, environmental, and safety standards.