1. Can you give us a brief overview of SGS and the services the company provides to help pharmaceutical companies test, develop, and manufacture cell and gene therapies?
As a leading global Testing, Inspection, and Certification (TIC) company, SGS supports pharmaceutical and biotech companies in the development of Cell and Gene Therapies (C>) by providing comprehensive testing of raw materials, drug substances, and drug products through all phases of product development. Our testing laboratories across the globe have a broad portfolio of techniques and expertise and operate at the highest quality under global GMP compliance. SGS also has a Phase 1 clinical unit and bioanalytical testing services that support C> products. SGS works collaboratively with C> developers utilizing a business model that best suits their needs.
2. What type of testing is required for cell and gene therapy products?
Like all biopharmaceutical products, C> products require testing throughout their production from testing of raw materials and production cell lines to in-process testing during manufacturing to the quality control release testing and stability of drug substance and drug product lots. Extensive testing is required to determine the identity, safety, purity and potency of these materials throughout all stages of production. SGS provides a comprehensive panel of analytical testing to support most stages of C> production that include evaluation of physicochemical properties such as appearance, pH and osmolality, determination of identity and content of raw materials and final products, quantitation and determination of both product and process impurities, testing of cell lines and final products for contamination with endotoxin and adventitious agents, and evaluation of potency through a variety of cell-based and in vitro methods.
3. How does testing cell and gene therapies play a crucial role in ensuring their safety and efficacy before they are administered to patients?
Like any other therapeutic agent, C>s, are evaluated for a number of critical attributes, including safety and efficacy, prior to patient administration. Since many C> products incorporate cellular production systems, potential contamination from host-related components and adventitious agents that pose a safety concern must be considered and carefully monitored by robust testing methods. Furthermore, general manufacturing processes also require assessment, including sterility, extractables and leachables, endotoxin, mycoplasma, and bioburden. Lastly, since many C>s involve changing the genetic make-up of the target cell (i.e. adding or editing genes), determining any off -target genetic modifications is becoming a key part of product safety. In addition to carefully evaluating the safety of a product, measuring a products potency is key to ensuring its potential efficacy when administered to a patient. These potency assays often involve in vitro cell-based assays that can quantitatively measure the functional outcome of the therapy.
4. What are the potential risks and adverse effects associated with cell and gene therapies, and how does rigorous testing help in identifying and mitigating these risks?
Risk assessment of C> products relies heavily on a detailed understanding of the product, its mode of action and the manufacturing/delivery processes. These risks include contamination by harmful agents (biologic and chemical) that stem from the raw materials, cell lines, and production process. Additionally, there are risks associated with off -target effects of the product, undesired immunogenicity that can lead to reduced product efficacy or cross reactivity, heredity implications, as well as potential passing of vector from patient to an untreated individual. Most of these risks, however, can be mitigated by thoroughly evaluating the quality and consistency of cell lines and raw materials; screening cell lines for adventitious agents, such as viral, bacterial, mycoplasma, fungi, prions, or parasites, and developing sensitive methods for evaluating any off -target impacts of the product.
5. In what ways can testing cell and gene therapies help researchers and clinicians gain valuable insights into the mechanisms of action and optimal dosing regimens for these innovative treatments?
Evaluating the potency of C> as part of release testing and stability is critical for understanding the product dose level required to elicit the desired impact in a cell. These assays usually involve an in vitro cell-based assay where the cells are treated with varying dose levels of product followed by a quantitative readout of the desired functional impact of the therapy on the cell. As the products progress through the clinical evaluation, this potency assay can be correlated with the clinical outcome influencing dose level and frequency.
6. What are the long-term implications of inadequate testing or skipping essential preclinical and clinical trials when it comes to cell and gene therapies?
While long-term risks require evaluation for many therapeutic classes, C>’s may be particularly prone to such events since many are intended to achieve a prolonged response and, as such, long-term exposure may produce unpredictable or unexpected delayed negative consequences for the patient. As such, comprehensive analytical and pre-clinical testing is critical in order to minimize delayed risks such as malignancy, impaired gene function, autoimmune-like reactions, reactivation after latency and infection, and resistant infections.
7. Looking ahead how will SGS continue to bring innovation and value to its customers who are developing cutting edge treatments such as cell and gene therapies?
Since many of the technologies being developed for C> are relatively new and only now being tested clinically, the understanding of how their quality attributes contribute to their safety and efficacy is constantly evolving. SGS’s collaborative approach in client interactions allows us to continually improve assays sensitivity and robustness, as well as develop new methods to meet regulatory needs. Furthermore, SGS recognizes the promising future of C> products in helping patients with debilitating and previously untreatable diseases and the need for rapid but accurate and sensitive testing. To meet this need, SGS has invested in state of-the-art equipment and personnel with specialized expertise to reduce assay turn-around-times without sacrificing quality.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special
offers from American Pharmaceutical Review delivered to your inbox!
Sign up now!