Clinical translation remains a barrier to the widespread application of cell-based therapeutics. Akron can help you successfully navigate the complex regulatory landscape for advanced biologicals and cell-based therapies.
cGMP Manufacturing Guidelines
There is huge potential and market interest in emerging cell therapies that are in clinical development for treating currently incurable conditions. However, the translation of cell therapies from bench to bedside represents a significant challenge. All drugs and biologics, including cell therapies, administered to human recipients are required to be manufactured in accordance with current Good Manufacturing Practice (cGMP). Unlike small-molecule pharmaceuticals, cells and stem cells are living entities that cannot be chemically synthesized; therefore, unique considerations must be given to the donor and source of the cells and subsequent processing.
Expectations for cGMP
GMPs cover manufacturing, controls, testing, and documentation and are the minimal standards. Within the U.S., as a product progresses through clinical development, the applicant must have full product characterization in place (21 CFR 610) and adhere to full cGMP (21 CFR 210, 211) before initiation of a Phase III trial.
Key Elements of cGMP
• Facility Designed to Control Operations
• Quality Control and Assurance Systems
• Adequate Documentation and Records
• Validated Production and Process Controls
• Equipment Calibration and Maintenance
• Personnel Training and Certification
• Environmental Monitoring
Chemistry, Manufacturing, and Controls
Chemistry, Manufacturing, and Controls (CMC) refers to all of the processes and reagents used in drug product manufacturing and all testing that is conducted on the drug product. In short, the CMC section addresses how the product is made and what is used to make the product. How the product is made includes processing and manufacturing; whereas, what is used to make the product encompasses the cell or tissue source (donor), and the entire history of reagents, components, and manufacturing equipment used to derive the drug product. Testing of the product includes both safety and quality tests. Safety testing includes sterility, endotoxin, and mycoplasma tests. Quality testing covers viability, identity, purity, stability, and potency. Other controls include product container labels, tracking, and product comparability tests.
Because the cells are isolated from a donor, they carry the risk of disease agents that may be present in the donor. Both the U.S. and EU have undertaken measures to regulate cells and stem cells derived from donor tissue that are intended for clinical applications. Within the U.S. the use of human tissue for clinical applications is governed by Good Tissue Practice (GTP) and in the EU it is regulated by the Human Tissue Act (HTA).
Derivation and Processing
The cell source and level of processing undertaken dictate the level of regulation. Autologous procedures carried out within the same surgical procedure or involving minimal manipulations, such as washing and cryopreservation, attract minimal regulation. In contrast, allogeneic procedures often involve cell culture and scale-up manufacture of the cellular product, which involves the highest regulatory demands on quality and process control.
Understanding Stem Cell Treatment Strategies
Scale-Up GMP Manufacturing
Generally more applicable to allogeneic cell therapy approaches, scale-up manufacture enables large numbers of patients to be treated from cells derived from a single donor. Scale-up manufacturing may involve the preparation of one cell bank from a single donor to treat a limited number of patients. On the other hand, a multi-tiered banking approach allows for much larger numbers of patients to be treated.
How Can We Help?
Akron offers an extensive array of GMP-manufactured reagents and our in-house manufacturing capability means that we can make anything you need to the highest standard. Furthermore, we can assemble all the reagents needed into a ready-to-use validated kit. GMP Manufacturing Kits are formulated to maximize stable growth of the target cell type to be manufactured and ensure compliance with the regulatory territory in which the product will be tested and commercialized clinically.