Quality biospecimens are make-or-break for scientists developing diagnostics and therapeutics. Many programs have been built upon specimens that lacked the required data and quality assurances necessary to support and gain regulatory clearance. To mitigate such risks, we have compiled a list of top considerations.
Many R&D scientists have acquired patient specimens through brokers who cannot certify sample handling, processing, and chain of custody. The unfortunate result is that products developed using those specimens are not clearing downstream regulatory hurdles and research needs. As a research scientist, it is vital to verify that specimens are collected under an IRB-approved protocol, with documented processing and handling procedures and chain of custody. Ask your specimen provider for proof of their IRB-approved protocols, chain-of-custody documentation, policy and documentation of freeze-thaw cycles, and relevant licensing, including FDA, IRB, HIPPA, and GXP.
Biospecimens are accompanied by relevant data sets that will initially be utilized by scientists and may eventually be purposed by clinical teams to support a regulatory application. Caution should be taken in this practice, as it has been observed that the integrity of data can be questioned. A common practice of specimen providers is the acceptance of self-reported or unconfirmed data (i.e., ICD codes) in place of data documented by healthcare providers, and supported by verifiable source records. The risk of accepting patient-reported information is that data integrity may be confounded by patient confusion, differences in interpretation of questions, and even dishonesty. We advise all of our clients to mitigate these risks by pursuing biospecimens collected and documented by healthcare professionals. Ask your supplier to explain their monitoring processes, including requesting redacted copies of monitoring records and reports. A supplier’s willingness and ability to provide this type of documentation will strengthen your confidence and trust in your specimen provider.
It is recommended that you maintain copies of compliance, licenses, and certification records related to products and services from each of your providers. Suppliers that are unable to provide this documentation should be avoided as it is evidence of a lack of operational quality standards. Additionally, where testing data is a key element of characterizing a biospecimen, diagnostics developers should require that the labs producing these results are CAP and CLIA certified.
Many researchers require further processing of biospecimens to match their intended use. Much of this bioprocessing is performed by the provider, making it important to verify the safety level and quality procedures of the provider. For example, if you require whole blood collected from COVID-19 patients to be processed to plasma and aliquoted, you should confirm that the laboratory has BSL2 certification and is following GLP. If you require isolation of the COVID-19 virus in culture, you must confirm the provider’s laboratory is certified BSL3 and GMP compliant. Confirmation that these quality and safety measures are in place should be verified and documented.
When planning for biospecimen acquisition, we advise creating a formal biospecimen plan that documents the current and downstream future use. If the end use or analysis of the biospecimen will involve genetic testing for example, it is vital that the consent obtained for the biospecimen collection permits this use. It is recommended that you obtain a blinded copy of the ICFs utilized for the specimen collection from each supplier. Consider the fact that specimen brokers tend to have different consents based on where they procured the specimens, creating a difficult, if not impossible, trail for verification in the future.
It is just as important to review the actual IRB-approved protocol used for the specimen collection. Ensure your use case is covered in the protocol intent and design.
Each type of research requires its own data set. Before choosing your specimens, confirm that a detailed certificate of analysis is provided containing the required data to support your intended research. For example, if your assay requires cells with a specific HLA type, you’ll need to make sure that your cells carry an HLA certificate. For the greatest flexibility, limit specimens to those that have been certified for multiple assays. This will allow you to pursue new lines of inquiry using the same cells.
Data harmonization is one of the most frustrating issues brought up by data scientists as they try to make research decisions. When samples are procured with inconsistent data or format, it makes using that data a nightmare. When building a specimen plan, request that the data be provided electronically, in a harmonized format, and ensure that the data is complete to facilitate downstream analysis needs. In diagnostic development, a minimum data set may include the assay method, test manufacturer, unit of measure, date of collection, date of testing, and related specificity testing. For therapeutics researchers, a data set may include demographics, treatment history, comorbidities, disease staging, disease classification, chemistries, and more. Be sure to understand how your organization might use these specimens to inform data requirements for future use.
Specimens that lack process control and experience variations in time between collection, transport, and processing run the risk of quality loss and value for planned research and development. Establish your standards and make it a requirement of your suppliers to provide proof or a statement affirming the processing and storage of the specimens they provide. While a specimen may have been collected with great care and intent, compliant biologistics are necessary from the clinic to the lab. Ensure your supplier follows IATA guidance and proper UN3373 Category B packaging during the transport of your specimens.
Your clinical study or research project may require a specific volume of biospecimen to conduct the analysis and data acquisition. However, careful planning should be taken to ensure “additional volume” is available (and provided) to account for any downstream requests, such as by scientists or the FDA to support any unexpected results or performance. Doing so in advance of procuring a specimen in your program will protect your efforts and head off frustration, waste, and delay.
Consider the impact that sample type will have on downstream needs such as package insert claims and regulatory applications. For example, the FDA may require the use of specimens from specific risk groups, such as healthcare workers, first degree relatives, or long-term care residents. While those requirements may not come due for several months, such specimens may be difficult to obtain when they are needed. Another consideration—not FDA required but end-use driven—is specimen handling. If you are intending to make a package insert claim that “specimens should be tested within 24 hours of collection,” then it would be important to ensure that you are not utilizing specimens obtained from a supplier who fulfills with remnant lab specimens, where the standard institutional holdback time period of 5 to 7 days is typical. Be sure to work with your team to really understand the needs prior to procuring or collecting patient specimens.
Many companies claim to process their samples, but be aware that not all sample processing is equal. Before you invest in cells or manufactured lots, brush up on industry standards and check that your supplier’s processes, products, and services are certified to meet them.
Jim Boushell is VP of Biospecimen Solutions at Precision for Medicine.