Dr Susan Darling, Ph.D., Senior Director of Biopharmaceutical Market and Product Management in the Global Biopharma and CE Business Unit of SCIEX, shares insight into what is fueling the growth of new drug modalities, key factors facilitating rapid development times and the role of advanced analytical technologies. âKo
Pharma under contract: What is fueling the growth and rapid advancement of new drug modalities?
Susan darling: Pre-COVID demands for faster, more accurate and automated methods were on the rise. A shift towards semi or fully continuous and flexible processes was already underway, but it was happening at a slow pace, which is common in the pharmaceutical industry, an industry opposed to change. COVID pressed the fast forward button, making the need for speed a necessity for vaccine development. The results obtained have shown that lead times can be safely and efficiently optimized using new generation methods.
Traditional vaccines are based on weakened or attenuated viruses that stimulate the production of antibodies that bind to the virus in question and prevent it from invading host cells. Although they provide good immune responses, it usually takes many years to develop and market them. More modern vaccines are derived from recombinant simulants of the relevant disease antigen in special forms which allow efficient administration, such as virus-like particles. These approaches, which have included new vaccines against Ebola and dengue, have shorter development times (1 to 2 years versus 4 to 5 years).
New genetic vaccines take a different approach to production and eliminate the need to work with live viruses. Approaches, including those based on naked DNA (plasmid), viral vectors and messenger RNA (mRNA) cause the production of viral proteins inside cells, using native protein translation machines and of post-translational modification in cells.
DNA and mRNA vaccines are typically administered as a lipid nanoparticle that enters human cells, which then produce the antigens that generate the desired immune response. With viral vector vaccines, the modified virus delivers the nucleic acid encoding the viral antigen to cells.
CP: What are the key factors facilitating rapid development times?
SOUTH DAKOTA: Once the genetic sequence of the infectious agent has been identified, genetic vaccines can be rapidly designed and processes for their expression developed and scaled up for clinical and commercial production. No cell bank or viral seed bank needs to be developed, and genetic vaccines require much lower doses. Production can therefore be achieved in a smaller footprint using single-use technologies, and scale-up is generally faster than with traditional viral vaccines.
It is important to note that unlike attenuated and subunit vaccines which require the development of a new process for each vaccine, with these genetic technologies only the creation of the genetic sequence of the targeted parts of the virus is required to generate a new vaccine. The formulation, production, packaging and even the safety profiles are almost identical from vaccine to vaccine. The ability to use robust and scalable platform processes that are almost identical from vaccine to vaccine dramatically reduces development times.
CP: What role do advanced analytical technologies play in drug development?
SOUTH DAKOTA: Access to robust and scalable analytical processes for DNA, viral vector and mRNA vaccines is a challenge today given the short timeframe to obtain analytical results. The cell-based functional tests and infectivity studies that have been used in the development of traditional vaccines can take days to weeks to generate results. However, the decision to advance a batch often needs to be made within 24 hours or less; manufacturers have to use limited information to make the decision to go ahead with a process and risk wasting time and an expensive product.
The development of consistent, scalable and rapid functional analytical methods is essential to improve the manufacture of genetic vaccines. Without rapid testing, the ability to fully understand all relevant process parameters and their impact on product quality attributes is limited, preventing the development of robust processes.
Advances in automation and data analysis have the potential to reduce analysis times and simplify analyzes while increasing consistency and accuracy. These tests must also have greater sensitivity and precision given the often low production volumes for genetic vaccines.
CP: How is this different from more traditional drug development methods?
SOUTH DAKOTA: To overcome the challenges associated with developing robust analytical solutions for genetic vaccines, many analytical technologies originally developed for protein therapies have been modified to meet the needs for evaluation of genetic vaccines. The experience is also drawn from the field of gene therapy. Other methods have been developed to meet the unique analytical needs presented by these new technologies.
Instrument manufacturers and software developers are committed to both modifying existing methods and developing new techniques that simplify and reduce the time required for the analysis of new modalities.
The aim is to provide robust, high throughput platform methods with high specificity, precision and resolution for the detection and quantification of biological compounds, even in the most complex and difficult samples, in order to that new drugs such as genetic vaccines can be brought to market safely. as quickly as possible.
CP: How is advanced analytical technology leveraged to ensure regulatory compliance in development and production?
SOUTH DAKOTA: Robust new assays based on mass spectrometry (MS) and capillary electrophoresis combined with laser-induced fluorescence (CE-LIF) and other detection methods quickly provide accurate and reproducible results for protein components and DNA genetics and viral vector vaccines (isoform plasmid, recombinant DNA sequencing, etc.) Liquid chromatography-MS / MS methods are useful for sequence confirmation and detection, separation and Rapid and reproducible sizing of mRNA, high resolution analysis of large fragments of the 5 ‘cap and 3’ poly-A tail, and confirmation of LNP composition.
Acoustic Ejection Mass Spectrometry (AEMS) eliminates tedious sample preparation, tedious liquid chromatography method development, and chromatographic run times while providing access to compound tuning and MS specificity at speeds up to broadband associated with plate readers.
Likewise, the direct coupling of capillary isoelectric-focused charge variant (cIEF) analysis with high-resolution MS enables rapid analysis of intact viral vector capsid proteins, allowing users to make more informed and timely decisions when ‘they are necessary.
All of these methods help accelerate critical decision making and in turn reduce development time and costs, both of which are critical to successful drug development today.
Susan Darling is Senior Director of Market Management and Biopharmaceuticals in the Global Biopharma and CE Business Unit of SCIEX. She is responsible for the growth in the Biopharma segment, the development and execution of the strategic direction, as well as the development of new products and workflows.