Large Molecules

Large Molecules Research and Development

Large molecules have been an important component of medical practice since the late nineteenth century, when the protective properties of passive immunization were discovered in blood transferred from pathogen-infected animals. Development of large molecules use well-defined bioprocess methods that enable mass production of proteins or antibodies using living cells (bacterial, yeast, plant, insect or mammalian).

large molecule phases

Large Molecule Discovery in Academic Institutions

Academic setting for large molecule research and development provides opportunities to effectively target novel diseases and its mechanisms. Researchers pursue projects and invest in unprofitable diseases such as Dengue and Malaria, high-risk projects which include unconventional disease targets and developing new tools or assays for biologics.

Industrial Large Molecule Discovery and Development

The patient is the focus in the industrial part of the large molecule and research and development. The target goal would be to help the patient overcome a disease and improve the quality of life. The development process of large molecules should be designed to ensure that biologics produced are effective, safe and available.


Understanding the Disease

Researchers work to unravel the underlying cause and discover the best targets for treating or preventing a disease. Targets are usually proteins in the patient's body which are associated with a disease or proteins in microorganisms causing a disease. The challenge is to identify which proteins are relevant, how those affected cells change a specific tissue, how the genes are altered and more importantly confirm its role in a disease. More commonly, diagnosis of a specific disease is done in animals but research is now turning into cell culture.

This knowledge is the basis for treating the problem and researchers from government, academic institutions and industry largely contribute to this knowledge base.

hybrid bioreactor

The hybrid bioreactor is a multi-functional bioreactor capable of doing four types of culture namely: adherent culture using microcarrier, adherent culture using macrocarrier, suspension culture and fermentation. The hybrid bioreactor is suitable for research and development experiments such as those for diagnosis or screening tests.

Target Identification

Once the underlying cause of a disease has been determined and understood, researchers select a promising molecule to become a potential medicine. This could be a gene or a protein that can interact and influence the target. There are a few ways to find a lead molecule. Nature itself offer many useful substances and interesting compounds for fighting disease. Some scientists use molecule modeling through an integrated software to identify any type of molecule that may work. Genetic engineering can also be used to produce disease-fighting biological molecules.

Early Safety Test

Initial tests are done to prove the safety of a certain “promising” molecule on how the body will process or accept it. Further tests are required if the drug candidate has required pharmacokinetics like appropriate absorption and metabolism by the human body. These experiments are executed with extraordinary diligence to minimize risks to human test subjects. The research is normally done by conducting studies in cells, tissues, and animal models. Animals play a critical role in the drug discovery process as well although much research and development can be done using various experiments or using computers. Governments and regulatory authorities require that medicines be tested in animals before they are tested in humans.

The key elements of large molecules in this phase:

Strain Selection and Optimization

A range of large molecule development includes peptides, proteins, monoclonal antibodies, bispecific antibodies, biosimilars, oligonucleotides, biomarkers, and antibody drug conjugates. For example, many mammalian cell lines have been explored for protein expression. Each cell line has a specific potential benefit as well as possible drawbacks. Knowing the right cell line as well as its optimization to produce the desired product is essential. The cell line will be the source of all future drug product and is then grown to a bioreactor where the growth and the metabolic activity of the large molecule are carefully monitored at all stages.



A single-use benchtop bioreactor for adherent cell culture at high cell density yield

hybrid bioreactor

Hybrid Bioreactor

A multiple-use bioreactor suitable for screening tests whether a specific cell line works best in adherent or suspension


The selection of media is most often relying on the method of cell culture, presence or absence of affinity tag for purification purposes, and more importantly, the cell type being cultured. Some cell lines require media with or without serum. The main objective on choosing the right media is to promote cell growth to obtain high cell density yield during expression experiments. To further enhance expression during experiments, the culture medium can be supplemented with small molecules to increase yield.

animal component free

Esco VacciXcell offers animal-component free media for specific cell lines and supplement media for cell culture optimization.

Process Development and Scale-up Capabilities

Most processes are either done in batch or continuous mode. Batch culture operations are performed and completed before the process moves to the next step while in continuous processing, processed products are moved to the next step as each unit is completed. Cells, whether suspended or adherent, are adaptable to a wide variety of culture conditions in small or large volumes. A significant increase in the growth surface area is equivalent to a large amount of the desired product can be harvested from the vessel. The problem with scaling up from a previous method is that the desired product should be expressed simultaneously without compromising it. Bioreactors are used for optimal mammalian or suspended cell growth. Typical bioreactors are capable of monitoring and optimizing environmental conditions to improve cell growth. In industrial setting for cell lines with relatively low overall yields, bioreactors represent as a great investment.


TideCell® runs in continuous mode for faster production with reliable product yield. It is equipped with a closed cell harvesting system for a cost-effective and efficient production.

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