CMC Support: Cell and Gene Therapy CRO Services
Detailed Chemistry, Manufacturing & Control (CMC) information submission is a critical part of your IND-submission irrespective of the class of therapeutic under investigation in order to validate the identity, purity, potency, viability, titers, potency, cell dose of your drug candidate. ASC offers expert CMC consultation and assay support for your investigational biotherapeutics: Lot release specifications, stability analysis, potency analysis at DNA/ RNA/ protein levels, titration, cGMP cell line characterization for cell therapies, we offer you a support and resources to navigate the guidelines provided by the FDA or other regulatory authorities to enable regulatory compliance.
Example of a Stability Analysis for a Hemophilia A Gene Therapy Product
|
Attribute |
0 |
12 weeks |
24 weeks |
36 weeks |
|
Sterility |
x |
x |
x |
x |
|
Genome Titer |
x |
x |
x |
x |
|
Appearance |
x |
x |
x |
x |
|
pH |
x |
x |
x |
x |
|
Infectivity/Potency |
x |
x |
x |
x |
|
Purity (SDS-Page) |
x |
x |
x |
x |
Stability performed on samples stored at ≤ -60°C
Cell and Gene Therapy drugs are revolutionizing the treatment of many diseases, the least of which is cancer therapy. For an investigational therapy to be approved for clinical trials, the FDA and other regulatory authorities require that sufficient Chemistry, Manufacturing, and Control (CMC) information should be provided for the investigational biologic. The CMC information should include detailed specifications and testing of all components used in the manufacturing of the therapeutic candidate for both preclinical and the proposed clinical formulation: Product Characterization, Manufacturing Procedures, and Product Testing. The CMC data should validate the identity, purity, potency, viability, titers, potency, cell dose, storage and stability, processing time, final formulation, release specifications, physical characteristics, and more.
- Vectors/ Constructs: A detailed description and characterization of the vector including the history, modifications, and relevant sequences of the vector/construct; production and purification
- Cells: Adequate pathogen and sterility testing, cell/ tissue type, cell collection methods, donor consent, comprehensive cell line characterization; preparation of the cell lines (genetic modifications, processing, differentiation from stem cells, etc.)
- Reagents/ Excipients: All components to be used in the final product should be listed in the IND.
Cell and Gene Therapy Applications:
- Chen, H., Shi, M., Gilam, A., Zheng, Q., Zhang, Y., Afrikanova, I., ... & Chen-Tsai, R. Y. (2019). Hemophilia A ameliorated in mice by CRISPR-based in vivo genome editing of human Factor VIII. Scientific reports, 9(1), 1-15.
Other CRO Services:
- Mace, E. M., Paust, S., Conte, M. I., Baxley, R. M., Schmit, M., Mukherjee, M., ... & Akdemir, Z. C. (2019). Human NK cell deficiency as a result of biallelic mutations in MCM10. bioRxiv, 825554.
- Baskfield, A., Li, R., Beers, J., Zou, J., Liu, C., & Zheng, W. (2019). Generation of an induced pluripotent stem cell line (TRNDi004-I) from a Niemann-Pick disease type B patient carrying a heterozygous mutation of p. L43_A44delLA in the SMPD1 gene. Stem cell research, 37, 101436.
- Hong, J., Xu, M., Li, R., Cheng, Y. S., Kouznetsova, J., Beers, J., ... & Zheng, W. (2019). Generation of an induced pluripotent stem cell line (TRNDi008-A) from a Hunter syndrome patient carrying a hemizygous 208insC mutation in the IDS gene. Stem cell research, 37, 101451.
- Cheng, Y. S., Li, R., Baskfield, A., Beers, J., Zou, J., Liu, C., & Zheng, W. (2019). A human induced pluripotent stem cell line (TRNDi007-B) from an infantile onset Pompe patient carrying p. R854X mutation in the GAA gene. Stem cell research, 37, 101435.
- Yang, S., Cheng, Y. S., Li, R., Pradhan, M., Hong, J., Beers, J., ... & Zheng, W. (2019). An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p. R401X mutation in the NGLY1 gene. Stem cell research, 39, 101496.
- Baskfield, A., Li, R., Beers, J., Zou, J., Liu, C., & Zheng, W. (2019). An induced pluripotent stem cell line (TRNDi009-C) from a Niemann-Pick disease type A patient carrying a heterozygous p. L302P (c. 905 T> C) mutation in the SMPD1 gene. Stem cell research, 38, 101461.
- Huang, W., Xu, M., Li, R., Baskfield, A., Kouznetsova, J., Beers, J., ... & Zheng, W. (2019). An induced pluripotent stem cell line (TRNDi006-A) from a MPS IIIB patient carrying homozygous mutation of p. Glu153Lys in the NAGLU gene. Stem Cell Research, 101427.
- Sundararaj, K. P., Rodgers, J., Angel, P., Wolf, B., & Nowling, T. K. (2020). Neuraminidase activity mediates IL-6 production through TLR4 and p38/ERK MAPK signaling in MRL/lpr mesangial cells. bioRxiv.
- Li, R., Baskfield, A., Lin, Y., Beers, J., Zou, J., Liu, C., ... & Zheng, W. (2019). Generation of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p. Q510P mutation in the PTPN11 gene. Stem cell research, 34, 101374.
- Li, R., Pradhan, M., Xu, M., Baskfield, A., Farkhondeh, A., Cheng, Y. S., ... & Rodems, S. (2018). Generation of an induced pluripotent stem cell line (TRNDi002-B) from a patient carrying compound heterozygous p. Q208X and p. G310G mutations in the NGLY1 gene. Stem Cell Research, 101362.
- Poli, M. C., Ebstein, F., Nicholas, S. K., de Guzman, M. M., Forbes, L. R., Chinn, I. K., ... & Coban-Akdemir, Z. H. (2018). Heterozygous Truncating Variants in POMP Escape Nonsense-Mediated Decay and Cause a Unique Immune Dysregulatory Syndrome. The American Journal of Human Genetics, 102, 1-17. https://doi.org/10.1016/j.ajhg.2018.04.010
Vozdek, R., Long, Y., & Ma, D. K. (2018). The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury. Sci. Signal., 11(550), eaat0138.
