By Dr. John Gebler, Director Strategic Biopharma Business Development
The impact of novel biologic modalities on the biopharmaceutical industry as well as on the popular belief of “what’s possible” in science and healthcare have been monumentous. Extraordinary events have made terms such as mRNA and CRISPR a part of our common social vocabulary outside scientific circles. Before the unprecedented COVID-19 pandemic in 2020, very few within the scientific community could fathom or predict the successful commercialization and effectiveness of mRNA vaccines. These vaccines have helped more than 5.5 billion people avoid serious COVID illness (Our World in Data). However, new generations of biologics are far from one-hit wonders. Since the recent commercial success and cost-effectiveness at scale of mRNA vaccines, new vaccine modalities are now being used to develop next-generation flu vaccines that are able to cover all possible strains. (A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes, 2022) Despite economic challenges we see across other industries, new drug modalities, including gene- and cell-based therapies, are experiencing rapid and robust growth (Katsnelson, 2022).
As new biologic modalities continue to advance rapidly, especially with increased investments, the analytical lab will need to evolve its capabilities to address new analytical characterization challenges to seize this historic moment in biopharma. The increased molecular size, the complexity of new biologics, and the evolving regulatory expectations place new burdens on core traditional analytical capabilities. At the same time, expectations to create and adopt robust, reproducible methods are required to mitigate risks and consistently deliver high-quality drugs.
Modern High Performance Liquid Chromatography (HPLC) and Ultra High-Performance Liquid Chromatography (UHPLC) columns have significantly improved over the past 15 years. The continued innovation is vital to addressing the challenges of complex characterization and the ability to deliver high-quality biologic drugs. Chromatographic column improvements substantially reduce waste and sample consumption, avoid repeat analysis, and ultimately reduce the time-to-market timeline. Phenomenex is committed to developing quality columns and sample preparation devices for emerging biologics like mRNA and gene therapy and growing its strong portfolio for traditional biologics such as recombinant proteins and peptides, monoclonal antibodies, antibodydrug conjugates, and oligonucleotides.
Phenomenex set the bar for oligonucleotide extraction and purification with sample preparation extraction kits called Clarity™ OTX™ in 2009. This solid phase extraction (SPE) solution isolates therapeutic oligonucleotides from interferences such as salts, sugars, large proteins, and genomic DNA that can be present in matrices such as plasma and tissue. Recent advancements of this product portfolio are 96-well plates with 25 and 2 mg of sorbent, designed for small volume samples but still capable of constantly yielding high recoveries.
In 2018, Phenomenex released their chromatographic column solutions for biologics under the brand BiozenTM. Biozen columns come in a variety of innovative particle morphologies and all are packed in bioinert titanium hardware to reduce the hydrophobic interactions between the column and analyte. The Core-Shell Technology is one of the particle morphologies that enables scientists to perform deeper protein characterization, such as peptide mapping, to identify product quality attributes and post-translational modifications, such as oxidations, deamidations, and phosphorylation. Additionally, this allows for high-resolution separation without extreme backpressure due to a specialized technology where a durable, homogeneous porous shell is grown on a solid silica core. Designed to facilitate a broader use of liquid chromatography pumps, the core-shell particle technology results in less band broadening compared to fully porous particles
Biozen™ dSEC-2, the next generation of size exclusion columns for antibodies and similar molecular mass modalities was introduced in 2021. This column features a robust diol-linked particle called dSEC and is available in various sizes to address discovery, development, and QC lab needs with consistent, reliable results. The dSEC particle pore size is controlled through a patent process to mitigate pore volume inconsistencies and resist column voiding. Thus, resulting in a robust and reliable column chemistry. The particle’s hydrophilic surface chemistry reduces hydrophobic interactions, allowing scientists to analyze proteins in a more native environment that maintains protein stability without compromising column performance. With the incorporation of titanium bio-inert surfaces, dSEC-2 holistically mitigates hydrophobic intertactions from a particle and hardware standpoint. The company is currently expanding the technology to focus on adeno-associated virus (AAV) characterization. With future Biozen columns, customers can accurately and quickly determine AAV capsid protein ratios and their aggregates as well as aggregates of larger proteins.
The holistic approach of using particle chemistry and hardware also has proven success in increasing reproducibility and reducing sample loss, particularly with hydrophilic molecules such as oligonucleotides. This approach is vital when characterizing mRNA samples (3’ poly A tail, and 5’ capping), as well as the developing and commercializing short, heavily modified oligo-based drugs such as siRNA/RNAi. The general mRNA market is expected to grow significantly over the next several years with new vaccines—both for the flu and ongoing COVID variants—along with therapeutic vaccines and gene silencing therapies.
As part of Phenomenex’s commitment to innovation, we recently opened the Phenomenex Innovation Center in Massachusetts, the latest dedication of significant resources to genomic medicines (e.g., mRNA and gene therapy) in addition to traditional biologics. This state-of-the-art lab is focused on biopharma R&D analytics and application development for traditional and emerging modalities. Matthew Turner, Phenomenex President, says “with this new lab, we have the opportunity to work within this innovative ecosystem to push our technology to the next level—and this helps us better support our customers who are working on some of the world’s toughest problems.” The lab complements the Torrance-based application lab, Phenologix, and is a vital addition to their growing list of globally located labs. Thus, expanding collaborations with global leading scientists and thought leaders and excelling the biopharma vision and efforts.
Today’s biological advancements create an unprecedented opportunity to treat countless diseases, but the industry must innovate—with the right partners—to fulfill this promise. Phenomenex is the right partner who will continue to unlock new potentials—advanced insights on safety, quality, and efficacy—for the scientist on the front line of this new era of medicine.