5 major trends in biopharmaceutical development in 2021

The 5 major trends of biopharmaceutical development in 2021. Although 2020 is an incredible and very difficult year, biopharmaceuticals have also made remarkable achievements this year.

The development of new models from vaccine development to pharmaceutical research and development has changed the biopharmaceutical industry. Here, we reviewed the five major trends that affected the biopharmaceutical industry last year, and these trends will continue to affect the industry in 2021 and for a long time to come.

1 Biopharmaceutical analysis is more than ever

Traditional engineered proteins and monoclonal antibody drugs still account for a large proportion of the development of new biological agents, but the next generation of treatment methods, including cell and gene therapies, multispecific drugs, and gene vaccines and therapies, are experiencing explosive growth.

Therefore, there is a growing demand for highly sensitive analysis systems that can be used to quickly characterize multiple types of analytes with sensitivity, accuracy, and high resolution. These systems must be able to separate, detect, and identify multiple analytes simultaneously in complex matrices and a wide range of concentrations.

Generally, analytes have highly similar structures, for example, nanobodies that can be distinguished by only one or two deamidation effects; protein contaminants from host cells and culture media may have a negative impact on safety and efficacy, which also brings Here comes the challenge of analysis; using conventional ligand binding assays, it is impossible to develop an effective single assay that can analyze different host cell protein (HCP) profiles (up to 1000 or more in each host cell).

A simple, fast and effective technique with excellent separation ability and high precision. For example, capillary electrophoresis (CE) is increasingly used to check and confirm the purity, heterogeneity and glycan of all types of biopharmaceuticals Associate. Professional and standardized reagents and kits optimized for specific CE methods have also been produced, such as capillary isoelectric focusing (CIEF), capillary zone electrophoresis (CZE), CE sodium dodecyl sulfate (CE-SDS) and CE-laser Induced fluorescence (CE-LIF) provides a complete workflow and solutions that are both accurate and flexible enough for quality control applications.

CE is also combined with mass spectrometry methods for a series of analyses required during the development and commercialization of next-generation models. At the same time, facts have proved that liquid chromatography tandem mass spectrometry (LC-MS/MS) using independent data acquisition technology can provide more comprehensive coverage, analysis methods are also faster, simpler to develop, and are used for better biotransformation And analyte characterization instructions. The analysis results are less false negatives, and the combined use of multiple reagents is cheaper. For example, the CE method can simultaneously detect HCPs from different organisms, and identify and quantify all HCPs in one injection, regardless of their concentration. In addition, it can be applied to any biological agent, including cell and gene therapy, without the need for longer development work.

2 Demand for new vaccines reaches the highest level in history

The COVID-19 pandemic has stimulated an unprecedented boom in the development of new vaccines. People are seeking a series of traditional and cutting-edge vaccine development methods. Vaccines based on naked DNA plasmids, viral vectors and mRNA genes utilize a powerful and scalable platform manufacturing concept and integrated process, which greatly shortens the time for vaccine development. With the rapid development and commercialization of these new vaccines, advanced analytical techniques play a vital role in ensuring the safety and effectiveness of these new vaccines.

Many analytical techniques originally developed for protein therapy have been modified or optimized to meet the needs of genetic vaccine evaluation. CE-LIF provides a fast, sensitive, reproducible and automated method for quantitative analysis of plasmid DNA isoforms and mRNA detection, isolation and size determination. It is important to consider which unique chemicals to analyze when completing routine or difficult automated sequencing of the Sanger genome.

LC-MS/MS can be used to identify and quantify HCP and other contaminants in viral vector capsids. It is also possible to use LC-MS/MS in combination with targeted lipidomics determination, multiple reaction monitoring (MRM) of experimental plans and rapid polarity switching to confirm the LNP composition of the formulated mRNA vaccine, which can be identified and quantified Nearly 1150 different polar and neutral lipids.

Regardless of the vaccine technology used, it is necessary to confirm the expression of the desired antigen and achieve a sufficient T cell response. The latest MS, CE-LIF, and multiple genome analysis can confirm support for manufacturers at all stages of development.

3 Unknown areas and treatments with new models

In addition to new genetic vaccines, many new therapies based on RNA and DNA, such as oligonucleotide antiviral drugs, viral and other gene therapies, various types of cells and genetically modified cell therapies, bispecific and trispecific Sexual antibody drugs. Today, bispecific T cell adaptors, peptibodies and nanobodies for conjugates are under development.

These new drug treatments overcome certain limitations of monoclonal antibodies (mAbs), such as the ability to bind to multiple sites at the same time, higher stability, and the ability to enter solid tissues and cross the blood-brain barrier. However, the complexity of these new models and processes may produce many variations. The titers of these therapeutic drugs are usually lower than mAbs (10-50%).

From the clone selection stage to production process development and commercial production, diversity and higher complexity have brought a greater burden to analysis. At low concentrations, it is necessary to distinguish molecules with smaller structural differences. Therefore, when developing analytical methods for these new methods, greater sensitivity and resolution are essential.

In order to overcome these challenges, the existing reliable mAb method is being optimized and adjusted to analyze the variation in the development process. For example, CE-SDS, cIEF, CZE, and rapid glycan analysis for peptide and nanobody analysis can be optimized by increasing the percentage of reagents in the sample, using different reagents, lowering the pH, and changing the temperature and time of the analysis.

The industry has been trying to find alternative orthogonal technologies that can solve the specific complexities of mAb variants (rather than just using improved mAb methods). Technologies such as capillary electrophoresis and mass spectrometry (CE-MS) can support the analysis of charge variants of intact Nanobodies, even if the mass difference is only 1-2 Daltons.

High-resolution mass spectrometry (HRMS) can ensure that the parent oligonucleotide and the primary and secondary metabolites of oligonucleotide antiviral drugs have sufficient resolution.

In order to characterize multispecificity at the subunit level, an LC-MS/MS system with differential mobility separation (DMS) technology can achieve higher throughput. This technology can separate protein subunits with a single injection and clearly identify each chain without chromatographic separation, thereby reducing the total time required to complete the study.

4 Patients need faster treatments

For developers of traditional and next-generation therapies, time to market is critical. For new therapies targeting specific genes, the urgency is even greater. Only the company that wins the market first can win in the fiercely competitive market.

Therefore, the key to improving the technological preparation of genes and other new therapies is to develop consistent, scalable, and high-yield platform methods and rapid analysis methods. Without fast analysis methods, it is impossible to fully understand all relevant process parameters and how they affect product quality attributes, which will prevent the development of good market processes.

Advances in automation and data analysis have the potential to reduce analysis time and simplify analysis, while improving consistency and accuracy. Given that the production of next-generation therapies is usually low, these assays must also have greater sensitivity and precision.

Facts have proved that the CE solution can provide the high sensitivity and high resolution required for GMP release for various applications. For example, CE-LIF can be used to determine the purity of AAV capsid protein. Its sensitivity is four orders of magnitude higher than that of the traditional SDS-polyacrylamide gel electrophoresis (PAGE) method, while using a smaller sample volume can improve throughput detection. .

5 Mature and reliable analytical methods

Pharmaceutical companies need to develop mature and qualified processes and analysis requirements, which provide a new model for monoclonal antibody drugs. Monoclonal antibody drugs have clearly defined process and analysis requirements. Developers of genes, cells, and other next-generation therapies lack platform solutions, regulatory guidelines, and skilled and experienced personnel, so they must create their own commercialization paths.

However, the U.S. Food and Drug Administration (FDA) continues to develop guidance documents to support the development and commercialization of these new life-changing drugs. The FDA encourages progress by creating opportunities to discuss the best ways to ensure the best product safety. Various alliances of technology providers, drug developers, and regulatory agencies are working together to modify existing methods and develop new technologies to simplify and reduce the time required to analyze new research. Combining the best analysis technology with the smartest treatment ideas will bring the latest and most effective treatment to patients as soon as possible

(source:internet, reference only)

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