Having Immediate Access to High Quality Biospecimens for Assay Analytical Validation Reduces Timelines and Costs!

​It never seems like there is enough time to develop an accurate, precise, and robust assay, and frequently the bottleneck is having access to high quality samples with enough quantity for all the analytical validation studies needed to validate the fit-for-purpose assay. For example, labs may require at least 20-30 samples with accompanying data for their desired biomarker to establish accuracy to an orthogonal method. Then, a handful of those samples spanning the reportable range will need enough volume to generate enough replicates for the individual validation studies, e.g., at least five replicates for multiple precision studies to validate a CLIA assay or an interfering substances study using three replicates per interfering substance spiked in with many different interfering substances to validate an investigational IVD.  Often, the sample acquisition timeline can be 12 months and the costs can be upwards of $2,000,000 depending on how rare the biomarker or disease indication. Sample types have to be considered, for example, bone marrow aspirates are challenging to acquire.    

Irrespective of whether the assay is being used for exploratory biomarker purposes or for patient selection for a clinical trial, clinically-derived samples are always needed to fully ensure that the assay is accurately and precisely performing and yielding robust test results. The assay development timelines depend on having the necessary biomarker-positive samples and disease indication to even start the analytical validation studies. Often the assay developer will purchase biospecimens from commercial vendors on behalf of the Pharma Sponsor and randomly screen them for the biomarker. This is not an optimal approach as often demographic and clinical characteristic enrichment clues from the Pharma partner’s preclinical and early-stage clinical studies are lost, and it can take much longer to identify biospecimens than if enrichment criteria had been applied. In addition, there is often only a focus on the primary specimens (e.g., blood, FFPE tissue blocks, FFPE tissue on slides, saliva, urine, etc.) during this sample acquisition process, and often the secondary samples are forgotten (e.g. extractions, lysates, library preparations, etc.). Pharma often does not retrieve the secondary specimens and ends up spending more money and time on sample acquisition for all their development projects. It is critical to store every primary specimen (e.g., sister tissue FFPE blocks) and secondary specimen available to maximize the utilization of that donor sample across all analytical validation studies.  

Given these sample sourcing issues, Boudicca Dx. advocates for managing biobanking in-house; management is entirely in-house and sample storage can be either in-house or off-site (e.g., samples are stored in a central biorepository). Biobanks should house diverse biospecimens, have easy access and transfer processes, and store detailed biomarker, clinical characteristics, demographics, and sample-related data for every single biospecimen.  Having control over all the primary and secondary specimens significantly reduces costs and timelines in addition to removing the reliance on one biospecimen or assay development provider for sample sourcing (significant risk to program if their sample sourcing timelines slip)!.

The most important consideration for any biobank is ensuring the privacy, consent, and safety of the patient who is graciously supplying the biospecimen. According to the National Comprehensive Cancer Network: “The researcher should provide the IRB with a protocol that outlines strategies to maintain confidentiality of identifiable data, including controls on storage, handling, and sharing of data, robust description of information technology plan to ensure that the data is protected and that the opportunity for a breach to occur is minimized.”[1] This confidentiality of identifiable data applies to both data associated with test results (e.g., biomarker data) as well as sample labels and identifiers that are used throughout the testing process to track the sample. It is critical to ensure not only that informed consent is given but is on-file. For example, when describing analytical validation biospecimens in an investigational device exemption submission to FDA for a significant risk investigational IVD. Consent must cover biobanking research and any future use (e.g., diagnostic assay development), as well as any special considerations, e.g., consent form language and IRB approval to address Genome-Wide Association Studies (GWAS). Any consent restrictions must be easily identified when retrieving biospecimens for an assay validation project and consent should always be confirmed when pulling samples for any analytical validation project. 

The biobank should have procedures on managing the collection, receipt, and accessioning of samples similar to clinical laboratories. There should be QA systems in place to ensure samples are accessioned, labeled, and stored in a traceable manner to enable seamless retrieval and distribution of samples and rapid identification of any sample-related QC issues. The QA department should establish SOPs, accreditation, conduct internal and external audits, and maintain all records, i.e. training, equipment maintenance, and chain of custody.  The biobank should proactively consider steps to preserve sample integrity long-term, for example making smaller aliquots of larger volume samples to avoid future freeze-thaw cycles, especially for those samples that may be used repetitively throughout a single validation study. In addition, all staff receiving samples into a biobank should be trained in handling bloodborne pathogens to ensure their safety. There should be procedures in place should a pathogen risk be identified, e.g. in case samples are from an individual with Creutzfeldt–Jakob disease or HIV/AIDs. 

It is critical to have physical QC measures in place, such as alarm systems for monitoring the temperature of cold storage units, restricted access for trained personnel, and a sample tracking system to record chain of custody throughout the sample lifecycle. When samples are distributed, there should be similar systems in place to ensure the continued integrity of the sample during its transit, such as stable temperature conditions, tamper seals, and sample manifests to aid in tracking samples from biobank to destination. In addition to sample integrity, safety should also be addressed when shipping potentially biohazardous materials. All local, state, or federal restrictions must be considered when transporting as well as any international requirements. All proper approvals must be in place before shipping specimens.

The last step to consider for the biobank is the return or destruction of samples or data. The biobank should have policies in place that state who has access to retrieve samples, which samples will be retained or destroyed, and how long each sample will be stored before destroying (e.g., based on sample stability). There should also be documentation in place to record who retrieved or destroyed the sample or data and in what manner.

Further considerations for biobanks are additional QA measures, space and logistics, and funding. The biobank needs to consider plans for future growth and whether it has space or resources to store the required sample types, as well as back-up storage units or contingency plans in case of disaster or power outages. Once the biobank has determined its design, purpose, and sample types, it needs to plan for its initial and long-term funding.    

Many Pharma and assay developer providers are unaware of ISO 20387:2018, which provides guidance on operating and maintaining a biobank for research and development. Following this guidance ensures that biobanks provide biological samples and data of the highest quality and demonstrates proficient operation to their end users and accreditors. There is guidance on establishing protocols for collecting, storing, and distributing biospecimens and their data, while also taking into account consent and privacy requirements.  Boudicca Dx recognizes the challenges that Pharma and assay development providers encounter when sourcing samples for analytical validation studies and has supported proactively implementing ISO 20387:2018 guidelines to establish a biobank that maintains specimens safely under the recommended storage conditions, with proper consent, and adheres to local, national, and international shipping guidelines for biological specimens. Having this biobank immediately available significantly reduces timelines. Boudicca Dx. can audit existing biobanks for ISO 20387:2018 compliance and support bringing the biobank up to these standards rapidly with minimal costs. 

Boudicca Dx has the expertise to support the design and build-out of an ISO 20387:2018 compliant biobank and can put all the regulatory and quality infrastructure in place within a very short time frame. In addition, Boudicca Dx. has extensive analytical validation expertise to ensure that all banked samples are of sufficient quality and quantity to support analytical validation studies. Boudicca Dx. has connections with commercial biospecimen vendors from working in the biobanking and biotech industry for over ten years and knows how to strategically source specimens quickly for analytical validation. Boudicca Dx. can manage the entire sample sourcing effort and has successfully done this for multiple Pharma and assay developer providers so they can focus on their product development.  In addition, Boudicca Dx. has access to software solutions that fully automate processes to manage and track samples, biomarker data, demographics, and clinical characteristics through its preferred providers. Reach out to kelly@boudiccadx.com to find out more about how Boudicca Dx. can support your biobanking needs and reduce your assay development timelines and costs for all your programs.
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[1] NCCN Points to Consider on the Best Practices for Biorepositories, Registries and Databases. https://www.nccn.org/orp/orp/default.aspx