As we discussed in our previous installment, the use of human biological samples in clinical trials is becoming increasingly important, especially as biopharmaceutical companies continue to develop more and more personalized, precision and genomic medicines. In order to maintain sample integrity, security and compliance, a strong understanding of the complex lifecycle of a human sample, and how to manage it, is critical. So, what exactly are the steps to managing a human sample through each phase of its lifespan?
The lifecycle of a sample starts even before the sample itself exists. The first step required to collect and use samples is to secure the appropriate informed consent. This includes determining the sample types (tissue, blood, DNA, etc.), frequencies and uses, which need to be captured in a clinical trial’s Informed Consent Form (ICF). Typically, the ICF is captured in paper form by the clinical trial site. This can make it difficult to find consent information when needed, and even harder to link it to an individual sample. As a result, delays to starting research can happen, or worse, improper sample use and potentially regulatory fines.
To avoid this, companies must be able to link ICF information as data attributes to the sample inventory, maintaining that link from sample collection, through analysis, long term storage and retrieval, to eventual destruction.
Collection at site
Once informed consent is complete, the actual sample collection can occur. Sample quality and data integrity starts at the site. Sites need the necessary equipment/packaging to collect, store and send the samples to the laboratory. Samples should be collected according to the sample plan in the protocol and in accordance with the ICF. However, challenges can occur, such as unexpected events causing the collection to deviate from the schedule, and unclear sample labelling.
These challenges can be overcome with a real-time tracking system that can track progress of samples against the sample plan and provide alerts for any deviations, and by maintaining clear, unique identification of samples to ensure they are linked to the appropriate patient and ICF. To better enable this, it’s beneficial to prepare and distribute laboratory kits to sites with all the ancillary supplies the site needs to perform the trial. Color-coded labeling and barcodes can simplify sample identification and eliminate the need for re-labelling and anonymization.
Distribution to laboratories
After collection, samples need to be appropriately packaged for sending to (central) laboratories. If samples need to cross borders, compliance with local customs regulations needs to be maintained. Having the expertise to manage the import/export process and troubleshoot any customs issues is essential.
Sample analysis and data reconciliation
The critical stage of a sample’s lifecycle is when it undergoes the appropriate tests at central or specialist laboratories. This is an important step because the analysis data from the testing is the outcome of all the other processes and contributes to the trial’s results. Sample data from multiple sources need to be cleaned and reconciled. Ultimately, the laboratory results need to be associated with other clinical data for the patient, in the Electronic Data Capture (EDC) system.
For potential future use, samples may be transferred to a biobank for long-term storage. This period can range up to 15 to 20 years. As with site-to-laboratory transfers, careful handling and import/export compliance are important at this stage of a sample’s life, to ensure integrity for future research.
Retrieval for future research
One of the benefits of human samples is that stored samples can be retrieved for new experiments, rather than recruiting a new patient population for a study. The challenge lies in finding the right samples and confirming that they have not been compromised. When a long-term sample inventory is well maintained, including the ICF information for each sample, it becomes simpler and faster to compile the necessary information for regulatory approval of new research, and to physically retrieve the right samples to commence the study.
In the final stage of a sample’s life, when it’s no longer deemed useful because its quality may have diminished or the allowed time for storage (stated in the ICF) has expired, it is sent for destruction. Maintaining the data necessary to determine this point in time, find the sample and enable updates of the system to indicate the end of life of the sample can help with this final stage.
Overall, maintaining compliance, integrity and quality oversight of a human biological sample during its entire lifetime presents sponsors with many challenges. With a strong understanding of these complexities, and the right management processes in place, sponsors can more efficiently manage their irreplaceable patient biological sample assets and maintain compliance with the changing regulations, and ultimately reduce clinical development cycles so promising new therapies can be delivered to patients in need sooner.