The U.S. Food and Drug Administration (FDA) established the Office of Tissues and Advanced Therapies (OTAT) to oversee the development and regulation of advanced therapy medicinal products (ATMPs). (ATMPs are a class of medicinal products that include gene therapies, cell therapies, and tissue-engineered products.) OTAT works with other FDA offices and centers to ensure that ATMPs are developed and regulated in a way that is consistent with the FDA’s mission to protect public health.
The FDA has established several regulatory pathways for ATMPs, including:
Investigational New Drug (IND) pathway: This pathway is for ATMPs that are in the early stages of development and are not yet approved for marketing. Sponsors of INDs must submit an IND application to the FDA, which includes data on the safety and effectiveness of the ATMP.
Biologics License Application (BLA) pathway: This pathway is for ATMPs that have completed clinical testing and are ready for marketing. Sponsors of BLAs must submit a BLA to the FDA, which includes data on the safety, effectiveness, and manufacturing of the ATMP.
Humanitarian Device Exemption (HDE) pathway: This pathway is for ATMPs that are intended to treat or diagnose rare diseases or conditions. Sponsors of HDE applications must submit an HDE application to the FDA, which includes data on the safety and effectiveness of the ATMP.
The FDA has also established guidelines for the development and testing of ATMPs, including guidelines on good manufacturing practices (GMPs), good tissue practices (GTPs), and good clinical practices (GCPs). These guidelines provide recommendations on how to ensure the quality, safety, and effectiveness of ATMPs. In summary, sponsors of ATMPs must follow FDA pathways and guidelines to ensure that their products are developed and regulated in a way that is consistent with the FDA’s mission to protect public health.
ATMPs and Single Cell Cloning
Single cell cloning is a useful technique for producing a population of genetically identical cells for use in the production of advanced therapy medicinal products (ATMPs), such as gene therapies, cell therapies, and tissue-engineered products. This technique helps to ensure the purity and consistency of the ATMP, which is important for the safety and effectiveness of the product.
Single cell cloning is typically performed using the following steps:
- Isolation of a single cell: The first step in single cell cloning is to isolate a single cell from a tissue sample. This can be done using techniques such as flow cytometry or laser capture microdissection. Alternatively, CellRaft® Technology can be used to improve the viability and number of single cell clones generated.
- Expansion of the single cell: Once the single cell has been isolated, it is cultured in a medium that allows it to divide and multiply. This process, called expansion, produces a population of cells that are genetically identical to the original single cell.
- Characterization of the cell population: The expanded cell population should be characterized to ensure that it is genetically identical and free of contaminants. This may involve DNA fingerprinting, DNA sequencing, or other techniques.
- Validation of the cell population: The expanded cell population should be validated to ensure that it is suitable for use in the production of ATMPs. Validation may involve testing the cell population under various conditions to ensure that it produces consistent and reproducible results.
- Production of the ATMP: The validated cell population is then used to produce the ATMP, which may involve transfecting the cells with a gene of interest or differentiating the cells into a specific cell type.
A Risk-based Approach for Cell Line Development, Manufacturing and Characterization of Genetically Engineered, Induced Pluripotent Stem Cell–derived Allogeneic Cell Therapies; Jennifer L. Dashnau, Qiong Xue, Monica Nelson, Eric Law, Lan Cao, Derek Hei. Cytotherapy. Volume 25, Issue 1, January 2023, Pages 1-13. Available online at: https://www.sciencedirect.com/science/article/pii/S1465324922007460.
Transitioning from Preclinical Evidence to Advanced Therapy Medicinal Product: A Spanish Experience; Paloma Gastelurrutia, Cristina Prat-Vidal, Joaquim Vives, Ruth Coll, Antoni Bayes-Genis,Carolina Gálvez-Montón. Frontiers in Cardiovascular Medicine, Volume 8, Article 604434, February 2021. Available online at: www.frontiersin.org.
U.S. Food and Drug Administration: www.fda.gov.
Kap Kumar, Ph.D., MBA
Kap Kumar has over 25 years of experience in the life sciences tools and reagents industry. He started in R&D and product development, where he launched products for cell biology and imaging applications. For the last 15 years, Kap has led strategic marketing, market development, and product management for a variety of companies, including Thermo Fisher Scientific (Life Technologies), Danaher (Beckman Coulter Life Sciences), Cell Signaling Technologies, Nexcelom Biosciences, and Avantor-VWR. Kap has diverse experience managing complex portfolios, including instruments, consumables, and reagents, both in early-stage and mature companies. Kap has a Ph.D. in Cell and Molecular Biology from Kent State University, a post-doctorate from Harvard Medical School, and an MBA from Babson College.