The Significance of ADC Drugs
Antibody-drug conjugates (ADCs) are humanized or human monoclonal antibodies that are chemically linked to highly cytotoxic small molecules (payloads), representing a new type of therapeutic approach. They have potential in cancer chemotherapy. This novel molecular platform based on antibodies can selectively deliver the effective cytotoxic payload to targeted cancer cells. Compared with traditional chemotherapy, it can enhance efficacy, reduce systemic toxicity, and has preferred pharmacokinetics (PK)/pharmacodynamics (PD) and biodistribution.
ADC drugs are hailed as the "magic bullets" in the field of tumor treatment. They combine the precise targeting of biological drugs with the efficient killing power of small molecule drugs, thus making them the focus of research and development, as well as a new hope for human tumor treatment. Currently, the UF/DF process of TFF has been widely applied in the downstream process of ADC, removing organic impurities, coupling-related impurities, and used for buffer replacement. TFF is a simple and reliable purification method that can achieve a high recovery rate of ADC of over 90%. Besides removing small molecules (organic impurities, coupling-related impurities), it can also remove all impurities related to the drug linker, as these compounds have a molecular weight significantly lower than the membrane pore size.
Process optimization of tangential flow filtration technology
The application of TFF technology in the preparation of ADC drugs requires meticulous process optimization, including controlling the liquid inlet pressure, reflux pressure, TMP, feed flow rate, reflux flow rate, ΔP, and filtrate outlet flow rate. Automatic control conditions can be changed based on pressure, flux, etc. conditions; and process switching can be automatically carried out according to concentration washing factor, conductivity, pH, UV, etc. conditions. Combined with various process controls, the endpoint of concentration and washing filtration can be determined. Through these key parameters, the best separation effect of ADC drugs can be achieved.
The Application of Tangential Flow Filtration in the Preparation of ADC Drugs
lConcentration and desalination of antibodies
Before the coupling reaction, the antibodies need to be concentrated and desalted. The TFF technology can be used for the concentration and desalting of ADC drug solutions, removing small molecule impurities and buffer components, and increasing the drug concentration to enhance the coupling efficiency.
lPurification of the product
After the coupling reaction, by choosing a filter membrane with an appropriate pore size, the TFF technology can remove unreacted antibodies and small molecule drugs, and separate ADCs from free toxins or antibodies through filter membranes of different pore sizes.
lBuffer replacement of the preparation
During the drug formulation stage, the TFF technology is employed to replace the buffer solution in the formulation, ensuring the stability and activity of the drug.
TFF technology serves as the cornerstone for achieving both high efficiency and stability in ADC drug preparation, representing a technical artistry that pursues process perfection. Amidst the rapid advancement of biopharmaceuticals, Yocell's tangential flow system provides robust support for ADC drug production through continuous technological innovation and refinement, propelling anti-tumor therapies toward a new era of greater precision and reliability.
