The Biopharmaceutical industry has achieved remarkable success and innovation these past few years, namely the first CAR-T cell therapy and antibody drug conjugate (ADC) approvals. Significantly, the global pandemic has fueled vaccine innovation with the rapid acceleration of RNA based COVID vaccines.
 
Currently, nine ADCs have received market approval, and in July 2020, the U.S. FDA approved the third CAR-T cell therapy, Tecartus, a cell-based gene therapy for treatment of mantle cell lymphoma (MCL). Additionally, to date, Pfizer-BioNTech’s COVID-19 Vaccine and Moderna’s COVID-19 Vaccine have been approved by the FDA for emergency use.
 
Along with these advances, there has been a significant increase in outsourcing, particularly related to vaccine manufacture and fill finish, as well as drug research and development, analytical services, and manufacturing.
 
As the number of advanced therapy medicinal products (ATMPs) in development continue to grow, new production strategies are helping to address the inherent development and manufacturing challenges associated with these therapies.
 
Alex Perieteanu, Ph.D., Director of Biopharmaceutical Services at SGS Life Sciences discusses the future of vaccines and biologics, how the pandemic is impacting outsourcing and operations, and the challenges and advances in manufacturing cell therapies. –KB
 
Contract Pharma: With the current COVID climate what do you anticipate for the future of vaccines and biologics?
 
Alex Perieteanu: As an outcome of COVID-19, we’ve entered a new era of vaccine and biological drug development. The pandemic has demanded unprecedented investment into vaccines, diagnostics, and treatments.  In a relatively short period of time, this has had a tremendous impact on the Biotechnology industry and the momentum is likely to continue.  Looking at vaccines alone, we’ve seen a rapid acceleration in LNP-mRNA based approaches, a promising technology, but one that had yet to mature to commercialization. That is, until recently, two COVID-19 vaccines have recently received FDA emergency use authorization (EUA) to combat COVID-19.
 
CP: How has the pandemic impacted outsourcing and operations? 
 
AP: Many organizations have had to carefully evaluate outsourcing strategies, internal capacities, priorities, and risks.  It’s of little surprise that we’ve seen an increase in demand across the board.  Whether it be for high priority activities related to Covid-19, supply chain diversification, or whether it is simply due to a needing to strategically outsource in order to manage internal capacities.   
 
CP: What capabilities will be needed down the road?
 
AP: A very difficult question, as almost everything is in demand.  With a tidal wave of COVID-19 related investigational new drug applications (INDs), the ability to support GMP level manufacturing as well as analytical testing, is and will be in high demand. Capabilities and experience in the nucleotide and vector-based delivery space (viral and non-viral) are going to be highly sought after in the near term and will continue until the market adjusts to an increased demand.
 
CP: Are there specific geographical markets that are key? 
 
AP: This pandemic has had a global impact. All markets with established capabilities are likely to see rapid growth in the sector; however, with such high demand, regions or nations whom otherwise do not have significant local production capabilities may look to fund, or partially nationalize some basic levels of production in order to ensure long term supply.
 
CP: In what services areas are you seeing the most growth?
 
AP: Development, clinical trials, and manufacturing are all integral parts of bringing a molecule to market, and one cannot be done without the other.  We’re seeing proportional growth in all areas. 
 
CP: With the advances in cell and gene therapies, what type of growth do you anticipate? Is the industry positioned to accommodate future growth?
 
AP: Cell and gene therapies, or advanced therapy medicinal products (ATMPs) offer groundbreaking new opportunities for the treatment of disease or injury.  While only a relatively small number of ATMPs have received regulatory approval, the number of active INDs in this category is expected to break 1,000 by the end of 2021.  
 
With a promise to revolutionize medicine, ATMPs are very likely to become a staple in 21st century medicine. The industry has been adapting to the emergence of ATMPs with significant investments in product development, and manufacturing technology. Ultimately, vector delivery systems, complexity of manufacturing, an evolving regulatory landscape, and finally cost remain at the crux these emerging technologies. 
 
CP: What are the current challenges developing and manufacturing these therapies and where are advances being made?
 
AP: A major challenge with gene therapies is genetic uptake, and the need for a vector to facilitate this delivery. The field is currently dominated by adeno-associated virus (AAV) delivery systems which are difficult to scale and many have fallen short of their supply demands for Phase II/III trials.  To help resolve this, a number of production strategies have been developed such as the use of Baculovirus and PiggyBac^TM expression systems, and Helper-Free Transfection systems. Non-viral based delivery systems such as lipid nanoparticles also show a high potential of resolving many manufacturing issues associated with viral based systems while delivering a highly scalable production solution.
 
Cell therapies are also challenged by complex manufacturing involving hundreds of distinct and often manual steps during manufacturing. Worse, for autologous therapies this is needed on a patient by patient basis.  Standardization, and automation technologies, such as Lonza’s Cocoon^TM are likely to drive simplified and standardized workflows.
 
Overall, ATMPs suffer from complex, and comparatively small scale manufacturing. Which, while not insurmountable, lends to another very real problem; Cost. Cell and gene therapies are among the most costly therapeutics available and dose regiments can reach costs in the hundreds of thousands.  Thus, cost is seen as one of the largest hindrances to commercial adoption.
 
 

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Alex Perieteanu, Ph.D. serves as the Director of Biopharmaceutical Services for SGS Toronto. Alex and his team of more than 85 scientists have successfully supported numerous IND submissions and BLA fillings; supporting CMC and R&D activities ranging from early-phase characterization, shelf-life stability, forced degradation, to analytical support during process validation, performance monitoring, and remediation activities. Dr. Perieteanu and his team have experience working on numerous biologics, and advanced therapy medicinal products and various stages in development and commercialization.  Alex brings expertise in Protein Structure and Function Biochemistry with a Ph.D in Biophysics and a focus on protein engineering. Alex has been with SGS for nearly 10 years, and before joining SGS was with Sanofi Pasteur Analytical R&D, and with the Structural Genomics Consortium.