2022 Annual Meeting Report: The Challenges of Safety Testing Strategies for Biotechnology-Derived Products

By Grace Chappell posted 04-01-2022 14:59


Biotechnology utilizes biological systems, living organisms (or parts of them), to develop or create new products. The Workshop Session “Safety Challenges and Development Strategies Unique to Biotechnology-Derived Products across Industries” during the 2022 SOT Annual Meeting and ToxExpo addressed challenges regarding safety testing strategies for biotechnology-derived products across the agriculture, food, and pharmaceutical industries.

Dr. Rene Vinas (Upside Foods) introduced the session, highlighting the broad application of the technologies and the resultant lifesaving therapeutics, disease-resistant crops, and reduction of greenhouse emissions, among other benefits. However, due to the novel and dynamic nature of these products, features of their safety may be unknown and current regulatory guidance may be limited or nonexistent.

Dr. Manojit Basu from CropLife America contrasted conventional vs. biotechnological crop improvement strategies. Conventional methods, such as plant breeding, have been used for centuries: crops we see every day, such as radishes, kohlrabi, and many others, were originally derived from wild mustard using breeding techniques. Genetic engineering uses nonconventional methods such as recombinant DNA to delete or insert DNA into a crop genome, or other modifications such as overexpression of a native gene. The weight of evidence for the safety of a biotech crop includes various aspects of the sources and stability of the engineered protein, and requires molecular characterization as well as characterization of the protein to demonstrate that the biotechnologically derived crop is substantially equivalent to a conventionally produced food crop. In the United States, the USDA, US EPA, and US FDA all play a role in regulating biotechnology food crops at different stages of their development and use and in consideration of risk of toxicity to the environment and ecosystem, as well as to human health. Overall, crops derived using biotechnology have been studied more than any other food product.

Next, Noreen Hobayan of BlueNalu presented on cell-cultured meat and seafood. Efforts to bring cell-cultured meat to market have been underway for some time: over 80 years ago, Winston Churchill stated that “we shall escape the absurdity of growing a whole chicken in order to eat the breast or wing, by growing these parts separately under a suitable medium. . . . The new foods will from the outset be practically indistinguishable from the natural products, and any changes will be so gradual as to escape observation.” We should expect meat made by growing cells isolated from an animal to become available to consumers in the very near future (Singapore is the only country to approve a cell-based meat product to date). The cell-cultured meat industry aims to address potential food insecurity and environmental impact as the world population grows, in addition to addressing animal welfare. Many companies have made a commitment to animal-free production, excluding additives such as fetal bovine serum. This commitment would thus also preclude animal toxicity texting. The US FDA and USDA have been very proactive in working with industry stakeholders to understand how to best regulate these products. Similar to biotech crops, producers of cell-cultured meat will likely aim to demonstrate substantial equivalence to “conventional” meat products.

Finally, session Chair Dr. Tod Harper presented on biotechnology-derived drugs, often called “biologics” or “large molecules,” among other names, which date back to the generation of penicillin by bacteria. Cells or viruses are now engineered to treat various symptoms and diseases, including cancer. One common issue for biologics is the development of anti-drug antibodies (ADAs) in animals during nonclinical safety assessments, when the immune system recognizes these large molecules as “foreign.” A lack of human relevance complicates data analysis of nonclinical data; ADAs can result in toxicities that may not be relevant to humans, and many of these biologics have specificity for a human peptide presentation or proteome processing. Given the rapid development and innovation of some biotechnology-derived therapeutics, coupled with the fact that the ICH Guideline (S6[R1]) for these products has not been updated in over 10 years, new strategies are needed for nonclinical safety assessments for many therapeutics.

Ultimately, cross-industry opportunities exist for learnings and progress in addressing challenges regarding safety testing and regulatory approval that are unique to biotechnology-derived products.

This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.

On-demand recordings of all Featured and Scientific Sessions delivered during the 2022 SOT Annual Meeting and ToxExpo will be available to meeting registrants in the SOT Event App and Online Planner after their conclusion, through July 31, 2022.