INDUSTRY LEADER INSIGHT:
Unlike conventional biologics, which have been commercialized for nearly three decades, the first approvals for cell and gene therapies in the United States came only recently, in 2017. As such, the market for these next-generation therapies are still emerging, and this developing and evolving industry is currently lacking in infrastructure, people with experience and expertise in this area, raw material availability and manufacturing and analytical technologies.
The existing manufacturing capacity for cell therapies, gene therapies and gene-mediated cell therapies remains insufficient at this time, but this infrastructure will likely be in place within the next three to five years. Similarly, the number of expert individuals with experience in gene and cell therapy process development and manufacturing falls short of what the industry needs to allow it to grow as quickly as it would like. Fortunately, many of these people are in school today and will be seeking employment in the next several years; others are gaining on-the-job experience.
Raw material supply constraints are a major concern for the cell and gene therapy market, with very long lead times existing for certain key materials. However, suppliers are working assiduously to expand their capabilities and capacities, and this issue should also be addressed within the next few years.
The biggest challenge lies in the areas of process development, manufacturing and analytical technologies. As was the case for biologic drugs 30 years ago, multiple methods for the production of different viral vectors and cell therapies exist. However, the industry is still experimenting to determine which platform is the best. For instance, adenovirus (AAV) vectors can be produced using triple plasmid, baculovirus and other methods.
Once the best platforms are determined — probably one or two for each specific process — and analytical techniques have been established, development and commercialization will be streamlined. Such maturation is likely to occur over the next 5–10 years.
Development of open-access platform technologies is fundamental to the philosophy of WuXi’s Founder, Chairman and Chief Executive Officer Dr. Ge Li. This approach stems from his vision that every drug can be made and every disease can be treated if companies, regardless of their size, have access to the right platforms and technologies.
Today, WuXi AppTec Group is a leading global pharmaceutical and medical device open-access capability and technology platform company with global operations. As an innovation-driven and customer-focused company, WuXi AppTec Group provides a broad and integrated portfolio of services to help our worldwide customers and partners shorten the discovery and development time and lower the cost of drug and medical device R&D through cost-effective and efficient solutions. With its industry-leading capabilities in small molecule R&D and manufacturing, cell therapy and gene therapy R&D and manufacturing and medical device testing, the WuXi platform is enabling more than 3,000 innovative collaborators from more than 30 countries to bring innovative healthcare products to patients and to fulfill WuXi AppTec Group’s dream that “every drug can be made and every disease can be treated.”
WuXi is focused on developing platform technologies that can be leveraged by our customers to streamline their process development and commercialization efforts. In the cell and gene therapy sector, the development of open-access platforms is essential for facilitating the growth of the industry and accelerating the timelines for new treatments to reach patients in need. They provide greater predictability and simplification in process development through the use of common materials and components, engagement with prequalified vendors and standardized record keeping. With these fundamental factors aligned, it is possible to move more rapidly from early stage to clinical development and help clients get to first-in-human trials and investigational new drug (IND) filings faster.
Today, there are a total of six pillars that form the overall WuXi AppTec Group, which consists of small molecule drug R&D and manufacturing, cell therapy and gene therapy, drug R&D and medical device
testing, biologics R&D and manufacturing, genomics and data platform, and in vitro and clinical diagnostics.
WuXi has been involved in cell therapy development and manufacturing on a small scale since 2004. We moved into the first new building constructed as part of a redevelopment project within the Navy Yard in Philadelphia, PA from Camden, NJ. Since then, we have produced over 6,000 successful GMP lots of cell therapies, cell banks and biologic products.
At the end of 2013, WuXi determined that the cell and gene therapy market would likely be an expansive market — and made a decision to be an active and leading player by properly investing in the market. Starting in 2014, WuXi started making significant investments in the market. In 2015, a 55,000-ft2 building for late-phase cell therapy manufacturing was constructed. In October 2016, the opening ceremony was held for a new 150,000-ft2 facility for the production of viral vectors and gene-mediated cell therapies.
With the three approvals of cell and gene therapies in the United States in 2017 and significant acquisitions in the advanced therapies space (Gilead Sciences’ purchase of Kite Pharma in late 2017 and Celgene’s acquisition of Juno Therapeutics in early 2018), it became clear that the industry had reached a tipping point. At the beginning of 2018, WuXi Advanced Therapies was established as a separate business unit.
As a contract development and manufacturing organization (CDMO), we believe it is our job to streamline the development and manufacturing cycle by establishing platforms that will drive the industry forward. As such, our vision has evolved from being an active player in the market to helping driving the growth of the advanced therapies industry. We intend to boost the market by enabling manufacturing platforms and other technologies, such as novel analytical methods. By doing so, we will make it possible for patients worldwide to gain access to these promising novel medicines as soon as possible.
WuXi Advanced Therapies is in the unique position of being able to leverage analytical development expertise in combination with manufacturing capabilities. In addition, we can conduct the vast array of analytical methods required for advanced therapies in-house, greatly reducing the need to ship samples to third parties.
This integrated capability offers numerous advantages to customers. The primary advantage is enhanced control, not only of analytical development, but also of development timelines. Eliminating the need to ship samples for testing greatly reduces the opportunity for error.
There are multiple opportunities for delay of timelines, including process development setbacks, lack of manufacturing capacity, problems with analytical development and testing and raw material supply issues. Delay in any of these areas can adversely affect project timelines. At WuXi Advanced Therapies, customers know we have full control of three of these four factors. For customers, integration of manufacturing and analytical capabilities also frees up limited resources that would otherwise be involved in managing third-party testing services.
CDMOs that can provide enhanced development support can better serve both their customers and patients. To this end, WuXi Advanced Therapies has been focused on building our process development and analytical development teams, installing both the workforce and expertise required to facilitate the forward movement of customer projects. With regard to process development, we have established platform processes for the adherent cell culture of lentiviral and adenoviral vectors and will soon be rolling out platform technologies for suspension cell culture as well.
This work has required establishing the equipment, buffers, media, plasmids and cell lines and then performing over 100 design-of-experiment (DoE) studies to exhaustively define a more robust process. We have also created standardized batch records that simplify record keeping and data analysis. Through this approach, it is possible to understand — with a far greater degree of predictability — how changes in key process variables will impact process performance.
Now when we start a new project for a customer, if we can put their gene of interest into our platform, we can more rapidly determine the changes required to get to the needed levels of titer and quality. Our investment of time, money and effort to develop these platform processes can significantly reduce development timelines with more robust and predictable processes.
Similarly, we have focused on creating platforms for testing. Unlike monoclonal antibodies and other protein-based biologics, for which testing methods are common and have been standardized, methods for the different viral vectors often have different requirements.
To reduce the complexity of analytical method development, where possible, tests that were typically semi-customized have now been standardized, while some methods that previously required complete customization for each project are now semi-custom assays. As a result, we are able to complete the assay development required for lentiviral and AAV vectors more quickly than in the past.
We have also invested heavily in the development of advanced analytical technologies (e.g., digital droplet PCR, next-generation sequencing) and have built up the expertise necessary for developing novel assays required for the monitoring and release of advanced therapies. One particular area of focus is the development of new technologies for evaluation of empty and full capsids, which requires innovation and creativity.
A final important attribute of our culture at WuXi Advanced Therapies is our constant desire to find new and better ways to support our customers. Historically, WuXi AppTec has been tuned to our clients and has typically been an early adopter of new technologies and strategies. We are always actively listening to our customers and the market and, whenever it is possible and makes sense, building out services that reflect this.
For instance, one driving impetus for entering into lentiviral vector manufacturing was requests by customers in the chimeric antigen receptor (CAR)-T cell space. These customers wanted to have just one service provider to produce the viral vector and perform the cell processing to simplify the supply chain and accelerate the development timeline. Recently, to meet customer needs for regulatory support, we have begun offering regulatory consulting services on the CMC side, helping companies with the IND and biologics license application (BLA) filings.
At WuXi Advanced Therapies, we are excited about the opportunities presented by the cell and gene therapy market, as well as other next-generation technologies like oncolytic viruses. We enjoy partnering with customers that are excited about their technology platforms and looking for a CDMO partner committed to accelerating their development timelines. We want to leverage our platform processes and integrated programs with their technology platforms to maximize the benefits to customers and, ultimately, to patients. We value working with clients that have potential game-changing technologies and need a strategic partner invested in bringing their technologies to patients in need.
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