How Similar is Similar Enough? A Sufficient Similarity Case Study with Ginkgo biloba Extract
Botanical dietary supplements are complex mixtures that can be highly variable in terms of both composition and quality, making safety evaluation difficult. A key challenge is determining how diverse products in the marketplace relate to reference samples that have been chemically and toxicologically characterized. Essentially, how similar does a product have to be in order to be well-represented by the tested reference sample? Ginkgo biloba extract (GBE) was used as a case study to develop and evaluate approaches for determining sufficient similarity. Toward that end, 26 GBE extracts were evaluated for chemical and biological-response similarity. Chemical similarity was assessed by comparing across chromatographic profiles (untargeted approach) and quantifying known marker compounds (targeted approach). Biological similarity was evaluated using both in vitro liver models and short-term rodent genomic studies. Statistical and data visualization methods guided by expert judgement were then used to make decisions about the similarity of products to the reference sample. A majority of the 26 GBE samples tested (62%) were consistently determined to be sufficiently similar to the reference sample across the various evaluation methods incorporating both chemical and biological data, while 27% were different from the reference GBE, and 12% were either similar or different depending on the method used. This case study demonstrated that approaches to evaluate sufficient similarity allow for critical evaluation of related, complex mixtures so that safety data from the tested reference can be applied to untested materials.