The preclinical bioanalysis of XDC drugs is not only a process of scientific exploration but also a challenge that requires exceptional skill and innovative thinking. Preclinical bioanalysis is a complex, multidimensional, and multi-step process that requires comprehensive evaluation of a drug’s pharmacokinetics, immunogenicity, safety, and efficacy. It requires researchers to possess a high level of expertise and innovation in drug design, sample processing, and analytical method development to ensure the accuracy and reliability of preclinical bioanalysis.
Medicilon’s Cloud Lecture Hall invites Ranran Liang, an experienced Project Manager from the Biopharmaceutical Analysis Department, to shed light on how to tackle the challenges encountered in XDC drug development and ensure precision at every step of the research process within this complex and meticulous field.
1. In the development of ADCs with Dxd analogs, which condition is better: 37°C or acidification? How should one choose?
Ranran Liang: In ADC analysis, no single method can be deemed absolutely superior. The choice of analytical method should be based on the specific properties and structure of the ADC molecule, as well as the differences from small molecule antibodies. Additionally, practical factors such as sample size are also the key determinants.
For example, when the sample size is limited, using a constant temperature of 37°C may not be the best option. Each analytical method has its inherent advantages and disadvantages. For instance, acidification might lead to molecular instability, while 37°C treatment could result in edge effects due to uneven heating. In practical analysis, we often find that for the same project, 37°C treatment may be completely unsuitable, while acidification performs well; conversely, different projects might require different processing methods.
2. When assessing the stability of PDCs, what aspects should be considered if the stability is poor?
Ranran Liang: Stability is a major challenge in the analysis of conjugated drugs and protein-peptide drugs. To effectively analyze these drugs, we need to identify the key periods that lead to instability. First, we need to identify the specific stage at which the drug becomes unstable. If the drug starts to degrade immediately after sample collection, we should add stabilizers during collection to protect the drug’s structure. This helps maintain the drug’s integrity until the analysis is completed. If the drug is unstable during the analysis, we need to take measures to minimize the impact of handling on the results. For example, we can perform operations on ice, or reduce the duration and intensity of vortexing. Additionally, adding protein stabilizers and enzymes to the sample processing buffer can help maintain the drug’s stability throughout the analysis process.
3. In the analysis of bispecific ADCs, is it necessary to develop two methods to detect the structure of the ADC?
Ranran Liang: In the detection of bispecific ADCs, it is not always necessary to use two analytical methods. Our choice should be based on a thorough understanding of the bispecific structure. First, we need to evaluate whether there is spatial interference between the two targets of the bispecific antibody and whether the attachment sites of the small molecules might affect the analysis results. If there is existing pharmacokinetic (PK) data for the bispecific antibody, we can use this data to select the most appropriate analytical method.
Whether you are an expert in the pharmaceutical industry or a curious newcomer to cutting-edge medical technology, Medicilon’s Cloud Lecture Hall will open a door to the future of drug development for you.
