DBS Sampling: If We Build It Will The Clinic Come?

I don’t think so. I don’t believe the advantages of DBS are compelling to the clinical organization. As the Bioanalysis Zone survey affirms, the bioanalytical community sees the primary advantages of DBS sampling as a cost-saving measure for the clinic. DBS sampling offers improved subject recruitment, ease of sampling, reduced collection volume, and ambient-temperature shipping and storage.

Combined, these would result in significant savings for a large-scale, multi-site, clinical program. So why then isn’t the clinic increasing pressure on the regulatory agencies and bioanalytical laboratories to accelerate the implementation of DBS sampling? I believe it is because cost savings during human trials is not the primary economic driver for the clinic in the current environment of increased regulatory and healthcare system scrutiny.

The primary economic driver for the design of a human clinical program is extending market exclusivity by reducing the timeline from first dose to regulatory submission, review and approval. The clinic values confidence in execution, confidence in bioanalysis, regulatory certainty and speed.

As noted in the survey, questions about sample integrity and spot homogeneity based on permutations of hematocrit, humidity, temperature variations and so on, will always produce a level of uncertainty for the clinic. Even if the entire spot is analyzed, respondents recognize that the difficulty or inability to create a homogenous addition of an internal standard, a homogeneous matrix dilution and the inability to perform a true incurred reanalysis are bioanalytical shortcomings and will always induce regulatory discomfort and increased scrutiny.

For these reasons I don’t believe dried spot sampling will ever achieve the confidence that the clinic and regulatory agencies have acquired for liquid samples. As a result, I believe that DBS-based submissions will always carry a higher risk of post-submission regulatory requests for additional data, cross-over studies, and longer approval times than traditional plasma-based submissions. Even if timelines from first dose to submission are not impacted by the DBS approach, it is unlikely the human clinic will on a routine basis be willing to take on the additional regulatory uncertainty and scrutiny introduced by DBS sampling solely for the sake of cost savings. Especially given that the clinical organization is typically the most risk adverse function in a company.

If we build it will the clinic come? I sincerely doubt it. The economic benefits of DBS for regulated pre-clinical and human trials are uncertain, while the bioanalytical shortcomings and regulatory risks are clear. It’s unlikely that DBS will ever be a routine sampling strategy in a clinical PK setting.

Nevertheless, the Bioanalysis Zone DBS survey respondents are optimistic that DBS will remain a viable bioanalytical sampling strategy, especially in the non-regulated study space. Here the impressive body of DBS research and characterization will serve the bioanalytical community well for the application of dried matrix spots as a “fit-for-purpose” microsampling strategy.