Fecha registrada: October 22 2015

Duration: 56 minutes 19 seconds

This webinar focuses on the use and application of differential scanning calorimetry (DSC) for structure and stability investigations of biopharmaceuticals, with an emphasis on monoclonal antibodies, in both early development and late stage products.

Case studies from biopharma will be presented, to demonstrate how DSC analysis is used in formulation development, stability, or biocomparability studies. Using simple analysis of transition temperatures (Tm) forTm-based stability ranking, to complex analysis including identification of individual structural domain transitions, DSC is versatile, and allows biopharmaceutical development at a faster development pace.

Table of contents
1. Welcome
01:37
2. Overview
00:33
3. Acknowledgements
00:36
4. Biopharmaceutical development challenge: Characterize protein higher order structure (HOS)
01:37
5. Biophysical techniques for analysis of protein structure
00:54
6. Biophysical characterization of proteins and higher order structure (HOS)
00:50
7. Complex task of protein stabilization
01:17
8. Existing ways to assess thermal stability: Subject protein solution to a temperature up-scan and monitor changes in a property
00:28
9. Why differential scanning calorimetry (DSC) as a protein thermal stability assay
01:22
10. Why DSC and thermal stability of biopharmaceuticals is important
01:36
11. Protein Stability
01:20
12. Tm…an indicator of stability
00:40
13. Protein Unfolding
00:00
14. Compare native, altered and mutant formsMicroCal DSC the universal stability monitor
00:36
15. Protein 2-state unfolding model
01:02
16. Criteria for thermodynamic analysis of DSC data?
00:48
17. Most large proteins (mAbs) proceed through “non-2-state” unfolding
00:54
18. DSC parameters
02:34
19. DSC gives multiple descriptors of unfolding transition
00:27
20. MicroCal VP-Capillary DSC with autosampler:
00:55
21. MicroCal VP-Capillary DSCLow sample consumption
00:28
22. Data from MicroCal VP-DSC (coin-shaped cell) compared to MicroCal VP-Capillary DSC cell: aggregation artifactMicroCal VP-DSC MicroCal VP Capillary DSC
01:50
23. MicroCal VP-DSC and MicroCal VP-Capillary DSC aggregation artifact
00:13
24. Differential scanning calorimetry (DSC) and biotherapeutics and biosimilars
00:29
25. DSC data: The simple, the complex, the complicated
01:12
26. The qualitative approach to DSC data
02:01
27. Most stable antibody constructs identified with DSC
00:28
28. Increase mAb stability through Histidine buffer selection
01:02
29. Correlation of DSC and SEC data for formulations development - pH screen
01:50
30. Correlation of DSC and SEC data for formulations development - excipient screen
00:27
31. Comparison of Native Proteins with their pH 3 and 6M Gdn Denatured Forms
01:13
32. DSC detects oxidation-induced structural changes in a mAb
01:11
33. DSC detects oxidation-induced structural changes in a mAb
01:28
34. Characteristic shape and area of DSC thermogram give means for assessing protein longevity
00:51
35. DSC data: The simple, the complex, the complicated
00:53
36. Understanding DSC method precision & sensitivity
00:53
37. Fit mAb with non-2-state model, obtain set of thermodynamic parameters
00:29
38. Establish criteria for comparability and characterization
01:25
39. Initial pH/buffer screening during preformulation development with DSC: Pre-formulation decision funnel utilizing Tm and T1/2
01:22
40. DSC data: The simple, the complex, the complicated
00:43
41. DSC can also be used to study the kinetic aspect of protein stability
01:00
42. Effect of oligosaccharides on mAb stability: batch-to-batch comparability via DSC
00:53
43. Effect of oligosaccharides on mAb stability: batch-to-batch comparability via DSC (continued)
00:45
44. The Ea values for each unfolding transition are comparable between batches
01:02
45. Applications of DSC to biopharmaceutical drug development
00:55
46. Built a comprehensive picture for protein stability under pharmaceutically-relevant conditions with DSC
00:42
47. Thank you for your attentionAny questions?
10:03
48. Contact Information
00:25