In drug development, human biologic samples are essential, particularly in the growing areas of personalized, precision and genomic medicine. The FDA approved a record number of personalized medicines in 2017, which now account for more than one in four New Drug Approvals. As the number of research samples grow, so do the logistic challenges throughout R&D processes.
 
PAREXEL recently launched a new Biological Sample Lifecycle Management service designed to help biopharmaceutical clients more efficiently manage their patient biological sample assets from informed consent and collection at site, through in-study lab analysis, data generation and future use. The offering combines PAREXEL’s laboratory logistics and genomic medicine services with BioFortis consent and sample tracking software.

The new offering is designed to maintain sample integrity, security and compliance with changing regulations and guidelines, and provides oversight of samples across labs, biorepositories and research and development facilities.
 
Sanjay Vyas, corporate vice president and global head of Clinical Trial Supplies and Logistics at PAREXEL discusses the significance of these biologic samples, the challenges associated with sample management and the regulatory implications. –KB
 
 
Contract Pharma: What’s the significance and how are these biologic samples being used in drug research and development?     
 
Sanjay Vyas: As precision medicine continues to become more prominent, the use of human biological samples, such as urine, blood, tissue, cells, DNA, RNA and protein, is increasing in clinical development. In fact, R&D spend in personalized treatments is expected to double in the next five years, and to support this goal, the number of research samples collected and stored will increase 20% to over 2 billion samples, according to the Visiongain Biobanking Market Forecast. For this reason, PAREXEL launched its Biological Sample Lifecycle Management service to provide biopharma clients with an efficient process for monitoring their sensitive biological sample assets. As regulatory requirements and guidelines continue to evolve because of this increase, PAREXEL’s offering is designed to help sponsors to comply with regulations.
 
Biological samples are used at several stages along the drug research and development process, including informed consent, laboratory analysis and storage for future research. For example, at the informed consent stage, samples can be used for general screening purposes, such as general patient eligibility and biomarker profiling. Throughout the trial, samples can be analyzed for PK/PD assessments, disease biomarker control, safety monitoring, etc. Future research purposes include translational and biomarker research and collecting additional data to secure market approval.
 
CP: What are the challenges associated with biologic sample management?
 
SV: There are a variety of challenges in the collection and management of biological samples. First, samples must be handled correctly. Samples travel through a complex ecosystem of laboratories, depositories, and research and development facilities in their lifespan, and it is crucial to track where samples are in the trajectory of the study schedule to ensure the link between the physical sample and resulting data is maintained. If they aren’t, it can compromise the ability for testing or trial results being compromised. In addition, it’s important to understand what the samples can and can’t be used for, based on the agreements made with the patient and documented in their Informed Consent Form (ICF).

There are also unexpected challenges that can occur, such as erroneous events causing schedule deviation or unclear sample labeling, to name a few. Samples stored in biobanks for future-use hold the promise of being retrieved and utilized for new research without the need to recruit patients for a new study. However, it can prove very difficult and time-consuming to find the right samples in the storage facility, and link them back to the ICF to be checked and submitted to the regulatory authorities to prove that the samples are permitted to be used for the new research. It’s been to known to take up to a year before the study could be started because the information is held in paper documents at the clinical trial sites.
 
CP: What is the logistic process for these samples?
 
SV: The first step required to collect and use samples is to secure the appropriate informed consent from the patient. 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. This document should clearly state the type of research the sample can be used for, how long it should be kept after the study and if it’s appropriate to be used for other research. Ideally, this document will be digital so companies can link ICF information and data attributes of the sample.
 
Once informed consent is complete, the actual sample collection can occur on-site. 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. However, a real-time tracking system is a valuable way for researchers to track the progress of samples against the plan and provide alerts for any deviations, allowing them to also maintain clear and unique identification of samples to ensure they are synced to the appropriate patient and ICF.
 
The critical stage of a sample’s lifecycle is when it undergoes the appropriate tests at central or specialist laboratories. This is an important stage because the analysis data from the testing is the outcome of all the other processes and contributes to the trial’s results. 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 then be transferred to a biobank for long-term storage. This period can range up to 15 to 20 years. 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.
 
CP: What are the compliance / regulatory implications for biologic samples?
 
SV: With the increase in sample use in clinical trials, regulatory requirements and guidelines are evolving to require full visibility into samples’ chain of custody and consent to ensure sample integrity and compliance are maintained. For example, the ICH E18 Genomic Sampling Methodologies for Future Use guidance strongly recommends that samples are stored long-term with appropriate infrastructure and IT to share chain of custody.  
 
The HHS’ Common Rule for the protection of human subjects focuses on the informed consent process to protect patient rights. The ISO Biobanking Guideline covers warranty of sample and data integrity including documented sample origin. Other guidelines and standards that are applicable to sample management include the draft EMA guideline on good pharmacogenomics practice and C-DISC standards for chain of custody documentation for genomic samples.