In today’s competitive environment and economic climate, the financial implications of being the first to file a promising new drug compound or chemical entity cannot be underestimated. Researchers and drug manufacturers are under even greater pressure to do more with less, and productivity and cost savings are at a premium. In the race to succeed, fresh hepatocytes (cells that mimic the properties of the liver and are used by researchers to evaluate the metabolism, drug-drug interaction and toxicity of drug candidates in a cost-effective manner) present a number of challenges.
Celsis International plc a provider of life science products and laboratory services to the pharmaceutical, biopharmaceutical and consumer products industries – outlines several key advantages of using cryopreserved plateable hepatocytes over fresh tissue for drug research.
1. Fewer Restrictions. The limitations of freshly isolated hepatocytes for studies like induction severely restrict the researcher’s choices for timing, demographics and retesting. Cryopreservation of these cells permits expanded investigation while retaining clinically significant activity. By removing constraints associated with tissue availability, cryopreservation allows for further testing of activity and genomic characterizations, re-testing from the same donor and scheduling at the researcher’s discretion.
2. Best of Both Worlds. Some cryopreserved hepatocyte preparations retain the fresh hepatocytes’ ability to attach to a collagen I coated matrix (cryo-plateable), extending their use for long-term culturing applications like induction. Both human and animal cryopreserved hepatocytes offer other benefits as well. For example, utilizing the entire liver produces larger lot sizes and, in the case of animals, reduces the number and frequency of animals sacrificed. Thus, cryo-plateable hepatocytes present an ideal system by offering the dual benefits of freshly isolated plateability and the efficiencies of cryopreservation.
3. Reduced Time Delays and Data Variability. As drug manufacturers strive to bring new life-saving drugs to market, time and predictability throughout the R&D process are essential. Even in the early pre-clinical phase, any unpredictability may slow the testing of early investigational compounds by causing scheduling delays that cost the manufacturer lost time and money. In many cases, freshly isolated hepatocytes may not be readily available due to reliance on liver donation which requires staff to remain on call for a liver, and may lead to potential weekend and holiday work. While liver resects from biopsies may improve availability, they are potentially dangerous as they do not include full serology reporting. In contrast, fully characterized cryopreserved hepatocytes can be immediately procured in large inventories and stored at the laboratory, controlling the scheduling of studies and accelerating time to market. Standard induction studies, as an example, typically may be completed 50 percent faster using cryo-plateable hepatocytes.
4. Improved Efficiency. Cryopreserved hepatocytes may be pre-characterized for enzyme activities, genotypes and for applications like induction or transport, representing another major advantage over fresh products. In fact, cryopreserved products may be obtained to meet specific donor requirements while maintaining high levels of viability, confluence or activity. Large inventories and a minimum five-year shelf-life allow researchers to repeat tests at future dates with no difference in product performance. Likewise, research being conducted at multiple sites can draw from the same product lot for consistent, simultaneous research worldwide.
5. FDA Equivalency. The use of cryopreserved hepatocytes is recognized as equivalent to using freshly isolated hepatocytes. Acknowledging this trend, the U.S. Food and Drug Administration (FDA) drafted a Guidance for Industry
In summary, the uncertainties associated with fresh hepatocytes – lack of availability of donors, difficulty matching profiles, unknown enzymatic activities, inability to repeat experiments from the same donor and time restrictions – often mean researchers may unknowingly rely on less-than-ideal donors or resected tissue without serology reporting. With cryopreserved hepatocytes, pharmaceutical manufacturers no longer have to compromise safety, scheduling or productivity. Given their many advantages, the benefits of using cryopreserved suspended and plateable hepatocytes outweigh those of fresh products and should be strongly considered.