The quest for personalized medicine adds to the complexity of today’s scientific questions. Drug discovery efforts require access to larger arrays of biosamples, and demand is exceeding supply, fueling the growth of the biobanking market.
“Humans are inherently variable, which is good for evolution but bad for drug discovery. More samples equal more reliable results. However, cost and ease of access tend to limit the number of samples used,” explained Paul Whittaker, Ph.D., director and unit head for preclinical biomarkers, respiratory disease area, Novartis.
Experts met at SMi Group’s recent biobanking conference to discuss the challenges the industry faces, from supply issues, standards development, and sample tracking across multiple organizations to potential uses for banked clinical trial samples.
Sources for human material are increasing, ranging from those that provide postmortem material, such as the International Institute for the Advancement of Medicine (IIAM), to consortia that provide samples from living donors with specific diseases, such as the Lung Tissue Research Consortium. Depending on source, varying amounts of donor information are supplied with the human materials.
The Medical Research Council and Association of the British Pharmaceutical Industry COPD consortium aims to identify more homogeneous groups of patients using extensive and standardized clinical and physiological testing.
“The term ‘well-phenotyped’ could mean an exhaustive list of clinical, physiological, and molecular parameters that would maximize use of human tissue for a range of experimental uses, or it could be a more restrictive set of parameters that are highly relevant to the particular hypothesis being tested,” continued Dr. Whittaker.
“For some lung diseases, like interstitial pulmonary fibrosis and chronic obstructive pulmonary disease, there is good access to high-quality, well-annotated material, and for others, such as pulmonary arterial hypertension, academic collaborations are the main way to access material.
“It is clear that no one biobank can meet all the needs for biomedical research and that biobank networks will be necessary to make collections more widely available.”
An exciting development is the emergence of virtual biobanking, where companies provide a single point of access to a range of biospecimens. Using networks of ethical sources, they find the tissues required to the specifications provided by the requester, and then deliver them to the requester. This streamlines the procurement of tissue and benefits all parties.
Maximizing Biospecimen Use
Biospecimens are most frequently used in drug discovery research. To answer questions about drug mechanisms in the patient, biospecimens obtained during clinical trials are invaluable.
Clinical trial protocols specifically state how collected samples will be used and how long they will be retained. Depending on consent parameters, biospecimens collected during a clinical trial are often discarded after the study report is finalized.
“Most companies are sampling more, increasing and building biorepositories,” commented Mads Roepke, Ph.D., senior scientific advisor, clinical pharmacology, LEO Pharma. “The discussion is what to use the samples for. Some companies impose strict internal barriers for use of samples, and bank samples only to use if safety or efficacy issues arise. Others are more collaborative across divisions, and use them for drug discovery and development in additional cross studies.
“Use of samples across studies requires special approval by the regulatory committees and consent from participants. When you are outside the parameters of the initial study protocol and wish to store patient samples for later studies with a new scope, you move into biobanking and the associated regulations, including questions of sample analysis and reporting.
“At LEO Pharma, we are currently looking at using biospecimens obtained from patients in one program for investigations in other programs where drug candidates with similar mechanisms of action and/or the same patient types are studied. Clinical data associated with the sample would be more specific to the disease. By maximizing the use of patient samples, we could increase our understanding of disease biology, and advance research on future therapeutics for the benefit of patients.”
Implementing End-to-End Processes
“Good quality assurance in biobanking is an end-to-end process,” remarked George Tokiwa, Ph.D., associate principal scientist, Merck Research Laboratories. “In a pharmaceutical company, you need to be sure that you plan, collect, process, track, and store future-use specimens in a manner that maximizes specimen utility, and minimizes risk to specimen integrity.”
Quality-management processes, documentation and the physical attributes of the specimen are all crucial. Specimen collection requires compliant, robust methodology and validated processes that safeguard specimen integrity. Good IT infrastructure, a robust comprehensive inventory system, specimen oversight/governance, and project management ensure chain of custody.
Merck utilizes processes to track specimen permissions, consent reconciliation, and other possible restrictions or attributes of the specimens, e.g., restricted to disease-specific use. Consent expiration dates are tracked, and specimens flagged and destroyed as required. In addition, since certain specimens or specimen analytes may be stable only for a finite period of time, these specimens are tracked and flagged as suspect when appropriate.
During the course of each clinical study, performance metrics are used for trend analysis to determine if intervention or remediation action is necessary. An example is future-use genetic specimen collection rates and DNA quality. Each study site’s performance is monitored and compared to expected collection rates, DNA yields, and quality.
“Biobanking specimens for long-term storage and future use can be an expensive proposition. We want to ensure maintenance of material that is of value,” continued Dr. Tokiwa. “We developed a specimen retention algorithm, a set of decision trees to assess the biorepositories’ inventories and determine how best to disposition the specimens. With appropriate stakeholders’ feedback we are able to objectively decide if specimens should be retained or discarded.”
Merck Research Laboratories recently signed a partnership agreement with the National Center for Cardiovascular Diseases Fuwai Hospital for collaboration on the development of China’s first biobank for cardiovascular and metabolic biosamples.