Lonza’s Jan Vertommen talks about building global manufacturing and development networks to advance innovative, life-saving therapies.
Tim Wright, Editor, Contract Pharma
Original link: https://www.contractpharma.com/issues/2021-09-01/view_features/global-outsourcing-trends/
Small and emerging pharma and biotech companies continue to rely on outsourcing partnerships to safely and quickly develop and manufacture a large portion of their small molecule development pipeline. Contract development and manufacturing organizations (CDMOs) like Lonza form integrated global manufacturing and development networks to meet their clients’ needs. To coordinate these networks, CDMOs must navigate the various regulations of the U.S., Europe, Japan, China and other countries. Additionally, the ongoing pandemic continues to create supply and demand issues and poses other logistical challenges.
How can a small and emerging biotech become an integral part of these integrated networks with limited resources and staff? Jan Vertommen, senior director and head of commercial development, drug substance at Lonza discusses how CDMOs provide their pharma partners with guidance, resources and access to global manufacturing and development capabilities. This enables them to safely and rapidly advance small molecule therapies into clinical trials, and to patients.
Contract Pharma: What are some of the challenges that you hear from your clients related to working within global manufacturing networks? Are emerging biotechs and larger companies facing different challenges?
Jan Vertommen: One of the major trends in global drug development in the past few years is that smaller companies are developing a greater proportion of the new molecules. Emerging or virtual biotech companies now own up to 80% of drug development pipeline. Rather than selling them to larger firms in early development, these companies are increasingly taking their molecules from clinical trials all the way through to commercialization by themselves. This has been a continuing trend over recent years due to the increased availability of funding as well as an increased focus on specialty meds, which have more defined patient populations and resultant decreased need for “big pharma” sales and distribution networks.
For small and emerging companies, the priorities are often speed and cost-effectiveness to meet timelines and budgets, particularly when their molecules are in early-phase development. However, smaller companies tend to lack the in-house development and manufacturing capabilities and/or capacity required to reach their goals as quickly and effectively as possible. As a result, they often look to external outsourcing partners to rapidly advance their innovative molecules and products.
A more recent trend is the increasing number of clinical trials being run in China by non-Chinese companies. Certain global pharmaceutical companies are moving early-phase development activities to China. And as development and manufacturing becomes more globally distributed and interconnected, access to high-quality global manufacturing networks will be more important than ever.
CP: What are the benefits or disadvantages, if any, of working with manufacturers based in Asia, versus Europe/North America?
JV: If a company runs clinical trials in China, working with a manufacturer based in China offers proximity, which can give shorter development timelines. Cost-effectiveness can play a role, but pharma and biotech leaders must also be sure that quality standards remain rigorously maintained. At Lonza, all our global manufacturing and development sites are held to the same high standards, regardless of region or country. That means development or manufacturing in Nansha, China is of the same quality as development or manufacturing in Visp, Switzerland.
No matter where you are in the world, tech transfer during development is always a risk. Different development partners may have different processes and expertise. That’s why working with a single outsourcing partner with a global network from early development up to commercial manufacturing should reduce the risk inherent to tech transfers and help advance products seamlessly from early phase to commercial production.
However, to achieve such benefits, CDMOs with extensive site networks—typically developed through the acquisition of smaller development or manufacturing service providers—must ensure that their site network has integrated quality management, data management systems and other processes. This is an ongoing focus at Lonza to ensure that the customer experience is the same regardless of the site or sites being utilized for any given project. In that respect, it is also important that the CDMO offers one contractual set-up that covers all activities at the different sites involved in a program and assures that transfers between sites are done under the responsibility of the CDMO to create a really integrated network experience for the customer. Having one global program manager at the CDMO overseeing and coordinating the activities throughout the CDMO network for a specific customer program is another key attribute of a truly integrated CDMO network approach.
CP: How can small, emerging biotech companies that operate out of a single country, typically with smaller staffs and limited resources, work efficiently and responsibly with external manufacturing partners who are based in different countries, or even on different continents?
JV: Pharma and biotech innovators may find benefits from working with a single external partner from clinical to commercial production having development and manufacturing capabilities on different continents. Avoiding tech transfers can reduce the time to clinic, and to market. Again, however, choosing the “right” CDMO partner can be a daunting challenge. Track record, phase-appropriate services, and truly integrated processes and site network are critical considerations.
Some CDMOs also have integrated offerings that might shorten the time it takes to reach clinical trials while reducing risk for partners. For example, Lonza’s SimpliFiH Solutions is an integrated suite of first-in-human services specifically for smaller biopharma companies and centered on bioavailability-challenged molecules which predominate today’s pipeline. SimpliFiH Solutions centers on a rapid technology selection methodology that requires a single gram of API to identify the best approach to improve poor bioavailability and solubility at phase one: particle size reduction, spray dried dispersion (SDD) technology, or liquid/lipid-based technology. Eliminating parallel technology evaluations saves precious API and time to phase I clinical trials.
Inherent to any first-in-human service offering must be ready access to the CDMO subject matter experts (SMEs) to ensure that timelines stay on track. Problem solving, complex synthesis, formulation design, and clinical trial strategies are but a few of the areas that our SMEs are routinely consulted on in support of customer projects. Finally, external service providers may also have expertise in terms of regulatory submissions, which may further streamline the development process and reduce the timeline from early phase clinical trials to market.
CP: Within the pharmaceutical industry, what role do CDMOs have in ensuring regulatory compliance across multiple countries, for example, between the U.S. and a network of EU manufacturers, or between Switzerland and a manufacturer in China?
There are inherent risks to working with a CDMO partner that lacks strong regulatory experience and expertise. This is particularly true for smaller companies who have limited in-house regulatory resources and require extensive assistance and counsel in regulatory submission documentation. Working with a partner that lacks regulatory experience can lead to lost time in the drug development process.
Part of the required regulatory expertise is knowledge of regulatory requirements in various markets. With global regulatory knowhow spanning the U.S., European, Japanese and Chinese markets, as well as other high-priority countries and regions, pharma and biotech innovators may be well positioned to enter new markets quickly. Lonza has supported 40% of accelerated small-molecule approvals with global regulatory agencies in the past five years.
CP: With development timelines becoming more compressed, speed to clinical trials has seldom been more important in the pharmaceutical industry. How can CDMOs ensure complex international manufacturing networks stay agile and responsive, while meeting customers’ clinical goals and their obligations to patient populations?
JV: Flexibility and integrated global operations are key. To properly serve global pharma and biotech innovators, CDMOs with capacity and expertise in different regions around the world are key. They must have a wide range of assets that can be scaled quickly in response to unexpected variance in demand through the development process and, later, the product’s commercial lifecycle. For example, if a customer’s molecule gets approved, their CDMO partner must have the capability and know-how to rapidly to scale up and commercialize.
CP: In navigating supply issues and other challenges related to the pandemic, what sort of innovative business models is Lonza developing to further integrate its global manufacturing and development network?
JV: Lonza is proposing several business models that support customer needs by further integrating our global development and manufacturing capabilities. First, we are developing contracts that offer access to capabilities and SMEs throughout our global network, so customers can access the capabilities that they need at any time. This flexibility helps us work with customers to respond quickly to changes in requirements or demand, such as after their product gains regulatory approval.
We are also making strategic investments and global expansions to increase development and manufacturing capabilities and capacity across small-, medium- and large-scale, helping to ensure that we have manufacturing capacity when and where it is needed. Most recently, in June 2021 we announced an investment of CHF 20 million to expand development and medium-scale manufacturing capabilities at our site in Nansha, China. The investment will allow customers to smoothly transition from early-phase to late-phase development and commercial manufacturing.
Other customers are interested in creating dedicated capacity for drug substance manufacture, which we typically call the “monoplant” model, to assure the highest level of flexibility and supply security. For instance, in December 2020, we announced an investment with the biotech company Aurinia to develop a state-of-the-art monoplant facility at our site in Visp, Switzerland. This facility is designed to assure supply security for voclosporin, for treatment of lupus nephritis and uveitis, to meet commercial demand in a flexible way.
