By: William Blake, Chief Technology Officer, Human-Based R&D
The demand for advanced therapeutics and new drug modalities is expected to explode in the coming decade. For example, more than 2,000 gene therapies and modified cell therapies are currently under development, along with 800-plus non-genetically modified cell therapies, according to the American Society of Gene & Cell Therapy.i And the development pipeline for monoclonal antibodies grew about 20% in 2022 to include 140 investigational drugs, estimates the Antibody Society.ii
While this is good news for patients awaiting treatments for complex diseases, it presents an immediate scalability challenge to biopharma leaders – one that University of Pennsylvania professor and CAR-T pioneer Dr. Carl June has referred to as a crisis waiting to happen. “My big worry is, what if we actually make … engineered cell therapies work for solid cancer?” June, who is on the Scientific Advisory Board for Danaher, said during the Danaher Genomic Medicines Summit held in December 2022 in Boston. “We just couldn’t meet the demand at this point.”
Indeed, biopharma leaders that are developing cell therapies and other potential cures for large patient populations will need to address bottlenecks in their research, development, and manufacturing processes to meet the expected demand. At the Danaher Life Sciences companies, we believe the solution is for the industry to embrace an “engineering biology” approach. This entails bolstering every stage of biopharma development with engineering principles and practices used more commonly in other industries.
Applying an engineering biology approach will require biopharma developers to adopt automation at every stage, from early discovery through manufacturing, and to lean on artificial intelligence to improve their processes. And it will demand that best practices be industrialized to improve and accelerate the innovation of new cures.
Engineering biology could also help solve one of the oldest and most vexing challenges in biopharma: the high rate of failure of drugs that look promising in phase 1 trials but never make it to market. Bringing in rigorous engineering processes at the earliest stages of discovery could drastically lower the attrition rate.
Enhancing early research with AI and automation
Several life sciences companies at Danaher Corporation — such as Molecular Devices, Leica Microsystems, SCIEX, IDBS, Beckman Coulter Life Sciences, Aldevron, and Cytiva — offer a wide array of products and services to support the adoption of engineering biology. They can partner closely with companies to make this transition, starting from the earliest stages of discovery and preclinical development.
One way to bring down the attrition rate in drug development is to industrialize the use of next-generation preclinical models. Molecular Devices offers tools for automating high-content screening workflows, and its AI-powered analytics can generate robust insights to improve the quality of preclinical data. Its Organoid Innovation Center offers researchers end-to-end solutions that streamline and scale the development of general tissue types, for example cerebral or intestinal organoids that can be used to screen potential drug candidates in human relevant contexts. With its December 2022 acquisition of Cellesce, a leading developer of industrial-scale patient-derived organoids (PDOs), Molecular Devices now offers custom organoid expansion services for customers that wish to outsource this step. Using proprietary bioreactor and bioprocess technology, Molecular Devices can manufacture reliable and predictive PDOs at scale, allowing biopharma researchers to quickly screen tens of thousands of potential therapies in 3D models that more accurately reflect human biology than lab animals do.iii
Researchers in early discovery who are searching for new drug targets or biomarkers to aid in optimizing patient selection for clinical trials can also benefit from automating basic research tasks, such as proteome analysis. Cell DIVE from Leica Microsystems enables multiplexing and automation to help researchers understand the tissue microenvironment with single-cell resolution. Leica’s technology can also enable Deep Visual Proteomics (DVP) to connect spatial imaging with protein measurements using a combination of AI, automated single-cell or single-nucleus laser microdissection and highly sensitive mass spectrometry. Researchers are using the new technique of DVP to characterize cell-type specific proteomes that hold promise in advancing efforts to identify potential future drug targets or diagnostic biomarkers.iv
The ability to couple innovative hardware with sophisticated data-processing software can further enhance drug discovery and development. SCIEX offers Acoustic Ejection Mass Spectrometry (AEMS), a technology that redefines high-throughput quantification workflows, allowing researchers to use non-invasive contactless sampling and analyze liquid samples at a speed of ~1Hz.v
By embedding artificial intelligence and machine learning into process data management, researchers can generate insight to optimize decision-making at all stages of development. IDBS Polar, for example, provides a single digital platform for designing, running and analyzing experiments, allowing researchers to capture data in context and automatically pull in data from multiple sources into an accessible central data backbone, eliminating time-consuming manual processes and the risk of harming data integrity.vi
Once therapeutic candidates are selected for clinical trials, engineering biology tools and processes can help clinical trial leaders streamline their analysis, introducing efficiencies that can greatly accelerate development. For example, the Cytobank platform from Beckman Coulter Life Sciences uses machine learning to automate the process of gating flow cytometry data, eliminating inconsistencies that can arise with manual processes and allowing more samples to be analyzed in less time.
Tapping engineering biology to scale up manufacturing
One of the biggest challenges in developing advanced therapeutics is establishing processes to ease the scale-up of manufacturing from early research to clinical trials to, ultimately, commercialization. Danaher’s Life Sciences companies can work with customers to put in place manufacturing solutions that span the entire biopharma lifecycle – and to standardize workflows to improve efficiency and the quality of the final product.
For example, Aldevron offers Nanoplasmid™ vectors, proteins and mRNA platforms for manufacturing genomic medicines at every stage, from research-grade to mass production. Aldevron supports biopharma innovators working on a range of advanced therapeutics, including CRISPR gene editing to address inherited diseases. Among its offerings is a full ribonucleoprotein (RNP) service that allows duly licensed scientists to optimize their CRISPR programs and streamline their reagents so they can more rapidly create their final drug product.
The use of adeno-associated viral (AAV) vectors for the delivery of gene therapies is expected to grow substantially, putting pressure on manufacturers to improve yields by addressing a common issue: capsids that are “empty,” meaning they do not contain the transferred gene and cannot produce a therapeutic benefit. Beckman Coulter Life Sciences offers ultracentrifugation-based analytical methods that can be used to characterize capsid fill at high sensitivities.
Cytiva can work with gene therapy manufacturers to standardize AAV manufacturing processes aimed at reducing the frequency of empty capsids. These protocols include purification with products such as Cytiva’s Capto Q chromatography resin, which allows the nearly complete separation of full and empty capsids.vii
Discovery and development of new advanced therapies to solve the unmet needs of large patient populations pose important challenges. By embracing principals of engineering, the biopharma industry will enable science at scale and be better prepared to address these challenges to meet the demand for advanced products like cell and gene therapies.
William Blake is Chief Technology Officer, Human-Based R&D for the Life Sciences companies at Danaher Corporation. He has extensive experience in the biotechnology industry, working to develop pioneering biomanufacturing, synthetic biology, and diagnostic technologies. He was previously the co-founder and chief technology officer of Pearl Bio, chief technology officer at Sherlock Biosciences, and has earlier career experience in strategy, business development and R&D leadership roles at the Wyss Institute at Harvard University, Greenlight Biosciences and Codon Devices. William earned his Ph.D. in Bioinformatics and M.S. in Biomedical Engineering from Boston University, and his B.S. in Biomedical Engineering from The Johns Hopkins University.
i https://asgct.org/global/documents/asgct_citeline-q4-2022-report_final.aspx
ii https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9728470/
iii https://www.moleculardevices.com/newsroom/news/proprietary-patient-derived-organoid-technology-with-acquisition-of-cellesce
iv https://www.nature.com/articles/s41587-022-01302-5#Sec6
v https://sciex.com/technology/acoustic-ejection-mass-spectrometry
vi https://www.idbs.com/polar/bioprocess/