Long before a clinician administers a drug or runs a new test, there is the arduous R&D cycle. Unfortunately, it’s rarely as streamlined as the one that just delivered COVID-19 vaccines in record-shattering time.
For most Americans, vaccines and drugs seem to spring wholly formed from clinical trials, which are becoming part of America’s everyday conversation. But before any vaccine or therapy hits the market, the less-visible pre-clinical research and development must be performed – from early bench research to understand targets and immune mechanisms, to proof of concept studies to identify potential drug and vaccine candidates, to animal studies to understand safety, to process development studies to establish how to effectively manufacture products for clinical trials.
Pre-clinical research and development takes time, seemingly a long time if you’re one of the patients awaiting a cure, a vaccine, or the right screen to diagnose mysterious symptoms. The process can be hampered by unnecessary delays, which mean treatments, diagnostics, cures, and vaccines get to hospitals and providers’ offices later than they otherwise might have.
Medical research relies on human biospecimens
Nearly all treatments, cures, vaccines, and diagnostics require the same scarce resource in the preclinical phase of R&D: the human biospecimen. Human biofluids, tissue, and cells need to be observed, characterized, and analyzed before and after a new drug candidate, vaccine, or diagnostic device is introduced. This work yields data that is often analyzed again, producing ever more astonishing results with the help of artificial intelligence.
The untold story of preclinical R&D is just how difficult it can be for research organizations, whether in hospital, pharma, or university settings, to get their hands on the right number of specific high-quality specimens they need.
At last reckoning, 4 out of 5 researchers told the National Cancer Institute that they’d limited the scope of their work because of their inability to obtain sufficient numbers of specific, high-quality specimens. We did an informal survey of our own in 2019 and found this was still the case.
Researchers’ specificity requirements are only rising. By specificity, I mean researchers need the right biospecimen (e.g. plasma, serum, or tissue) in the right form (e.g., fresh, frozen, or fixed) from a patient from the right demographic group with the right disease at the right stage with, perhaps, the right mutations or treatment outcomes.
For example, it generally is not enough for today’s researcher to study just any 50 breast cancer tissue specimens. In this era of precision medicine, a researcher might reasonably need 50 samples of tumor tissue from patients with metastatic, HER2-positive breast cancer, with a HER2 L755S mutation, refractory to Herceptin.
This complexity only begins to explain why improving biospecimen procurement has become a pivotal part of biomedical R&D.
Avoidable specimen procurement mistakes
While specimen suppliers hustle to find what you need, researchers can help themselves – and the ill patients who are waiting on cures – by avoiding common mistakes that sometimes slow down early-stage R&D. Here are some of the mistakes we’ve helped researchers avoid:
1. Assuming specimens are in stock – Researchers too often assume that commercial biobanks possess massive inventories of every conceivable human biospecimen one might need. Although millions of unused biofluid, cell, and tissue samples do exist out there, biospecimens are like books: The ones you don’t need, no matter how plentiful, are irrelevant. You may have to wait until they are randomly collected or set up a custom collection.
2. Failing to allow enough time to recruit providers – Unless the research organization needs only a few specimens, it likely needs to enlist multiple organizations – biobanks, biorepositories associated with large health care systems, clinical labs, pathology labs, blood centers, physicians’ offices, surgical centers, etc. – to contribute to the specimen collection they need. It takes time to find these organizations, develop relationships, and execute material and data use agreements. This step can easily take many months to more than a year per organization.
3. Unrealistic expectations – Too often, research organizations don’t understand the finer points of specimen collection and develop respective RFPs that may not be in line with standard of care. Consider a company working on a liquid biopsy project that incorporates the use of 20 ml of plasma each from hundreds of individual donors. Unfortunately, finding that amount of plasma in a biobank is like hitting the lottery. To get 20 ml of plasma from a patient, one needs to collect 50 ml of whole blood from that patient. This is the upper limit of the HHS guidelines for “minimal risk” blood collections; and therefore, if a patient has had blood collected as part of their clinical care, they would be disqualified from participating in the research donation. However, had the research organization requested a 30 mL blood donation, more patients would qualify, and collections could occur more quickly. Research organizations may be better served by changing their expectations based upon standard of care and existing research guidelines.
4. Slow IRB approval process – In addition to material and data use agreements, each specimen collection site requires ethics (IRB) approval, consent forms, and compliance audits. These steps can consume a lot of time and run up costs. Researchers need to perform due diligence on all sites or specimen brokers with whom they engage, especially on unusually low bidders. Failure to properly put compliance frameworks in place can introduce unnecessary risk and delay in the specimen procurement process.
5. Failure to plan time for kit building – Every custom specimen collection requires a special kit instructing clinicians how to collect required specimens in proper amounts and how to process them afterward. Detailed specifications and kit building can add time and complexity. This is especially true when kits require special tubes or media that may have long lead times.
6. Lack of training – Everyone collecting biospecimens needs to be trained in both the standard of care for collecting specimens and in the specific requirements of the study at hand. What if a junior staffer swabbing noses and throats in a parking lot for COVID-19 didn’t go deep enough? The swabs would be useless not only for testing but for research. Neglecting training can put years of work at risk.
7. Unrealistic collection parameters and timelines – It takes time for the right patients and specimens to come through the process in the right quantities. If you’re looking for, say, specific tumor tissue from a specific demographic, these patients have to appear in hospitals, award their consent, and undergo the surgeries on their schedules, not those of the researchers. Planning for extended collection timelines from the start can help manage expectations.
8. Failure to account for special requirements – Complexities like longitudinal specimen collections or the same-day delivery of specimens with specific test results that cannot be known for days after the specimen collection (e.g., fresh blood from patients pre-colonoscopy with polyps removed during the colonoscopy) add further complications for which more time and budget need to be built-in. Ditto for special processing, such as post-collection specimen sequencing.
Although biospecimens may not be the most celebrated resource in medical research, they are among the most important. Any handful of these very common mistakes may steal valuable time from providers and patients who need the next treatment, cure, vaccine, or diagnostic.
The best way to avoid these common biospecimen procurement mistakes is to engage with experienced specimen suppliers early in the project design phase to better plan for the biospecimen collection process. This will not only help you increase the chance of your project’s success, but also reduce your burden and red tape by shifting much of the work to the specimen supplier.
About Jill Mullan, Chief Operating Officer, iSpecimen
Jill is responsible for ensuring operational excellence throughout the company. In this position, she oversees iSpecimen’s supply partner programs and operations, human resources, marketing, corporate communications, and corporate strategy. She is also responsible for ensuring regulatory compliance, privacy and security across the company’s operations.
Jill has over 25 years of experience in operational management, strategy, and marketing. Before joining iSpecimen, Jill ran a consulting business to help companies develop business and product strategies, raise funds, create brands, and launch new products. Prior to that, Jill was on the founding team and Director of Marketing at Storigen Systems, where she built and ran the company’s marketing organization, developed the company’s brand identity and launched several successful products. She was also the Director of Product Marketing and Management at Avid Technology, managing the P&L for Avid’s $400M editing product line. Jill graduated with distinction from Cornell University with a BS in electrical engineering and received her MBA from Stanford University.
