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.
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:
Learn more about this technology.
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REFERENCES
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 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.
In the ongoing battle against antibiotic-resistant bacteria, or “superbugs,” scientists are constantly seeking innovative tools to understand the mechanisms of resistance and develop effective treatments. One such groundbreaking technology is shear flow systems, which have emerged as game-changers in microbiological research. By simulating the dynamic conditions of bacteria’s natural environments, such as the human body or food processing, shear flow systems provide unique insights into bacterial behavior and resistance mechanisms that traditional static methods simply cannot achieve. In this blog post, we’ll explore the benefits of using shear flow systems to combat antibiotic resistance and develop next-generation therapies.
Antibiotic resistance is a complex phenomenon influenced by a variety of factors, including genetic mutations, horizontal gene transfer, and the formation of biofilms. Traditional laboratory methods often fail to capture the dynamic nature of these processes, leading to incomplete or misleading results. Shear flow systems address this limitation by providing a more realistic environment for bacterial growth and interaction. Here’s how:
1. Mimicking Real-World Conditions
In the human body, bacteria are rarely in a static state. They are constantly exposed to fluid flow, such as blood circulation or urine flow, which influences their behavior and resistance mechanisms. Shear flow systems can replicate these conditions, allowing researchers to study how bacteria respond to antibiotics under realistic physiological conditions. This is critical for understanding how resistance develops and persists in vivo. This benefit was recently highlighted in a webinar presented by Dr. Katharina Richter, a microbiology researcher from the University of Adelaide in Australia. Using a high-throughput BioFlux Shear Flow System, Dr. Richter and her team were able to test 3 different methods of superbug treatments under physiological conditions.
2. Studying Biofilm Formation and Resistance
Biofilms—structured communities of bacteria encased in a protective matrix—are a major contributor to antibiotic resistance. Biofilms are notoriously difficult to treat because they shield bacteria from antibiotics and the immune system. Shear flow systems enable researchers to study biofilm formation in real time, observing how bacteria adhere to surfaces, form microcolonies, and develop resistance under flow conditions. For example, using a BioFlux, Dr. Richter was able to leverage high-resolution imaging to obtain unprecedented insight into the biofilm killing and prevention efficacy of a copper and diethyldithiocarbamate (DDC) combination nanoparticles¹. The group is currently investigating the use of a Cu-DDC infused gel that can be injected into wounds that are at high risk for chronic infection, such as hernia.
The study of biofilm communities presents unique challenges in experimental design and analysis. While mixed bacterial populations offer fascinating insights into microbial interactions and community dynamics, accurately characterizing and investigating these complex systems has previously required sophisticated and tedious technical approaches. Here, we will discuss advances in technology that have helped to simplify and streamline polymicrobial investigations.
Throughout the last decade, a trend for growing and assaying biofilms under shear flow has gained traction among microbiologists. The rationale for investigating biofilms under flow is multi-dimensional. A recent Cell Microsystems survey asked why microbiologists are using shear flow found that the top responses were:
Of the scientists surveyed, 40% indicated that they use a BioFlux Shear Flow System. This system provides unique advantages over other methods to induce shear stress, such as slide-based parallel plate flow chambers and benchtop rockers.
BioFlux uses microfluidic channels embedded onto the bottom of standard-sized 6, 24, or 48-well plates to create isolated and independent flow chambers where user-defined wall shear stress is initiated and maintained by digitally controlled air pressure. This not only simplifies the setup and experimental processes but also ensures that experiments are contained and do not contaminate the shear flow system.
Although shear flow has been thoroughly demonstrated to improve the biological relevance of biofilm investigations1, an often overlooked aspect of biofilm physiology is the significant role that multicellular aggregates play in biofilm formation2. When investigating Pseudomonas aeruginosa, it has been demonstrated that multicellular aggregates lead to faster biofilm formation and enhanced resistance to antimicrobials and immune responses3. In addition, multispecies microbial aggregates have been shown to dominate single cells in human saliva4. Together, these data show that aggregates are important areas of investigation because they are more likely to represent physiological biofilm formation and growth.
