FDORA, Regulatory Risk, and Sample Traceability - A Q&A with Edye Edens

Edye Edens is a licensed attorney with an international human rights, ethics, and health law background, who was in-house counsel for a decade with a major academic medical center. There, she focused on research administration and operations, FDA readiness, IRB/HRPP, clinical research compliance and quality assurance, grants/contracts, research misconduct, and oncology, before departing for the consulting world where she continues her work in these areas. Additionally, she teaches at IU’s McKinney School of Law and oversees the Hall Center for Law and Health’s Externship Program.

As an advocate for the role clinical trials play in advancing healthcare, she believes research compliance is essential to running efficient and ethical trials. 

In this interview, Edye discusses the recently released section 3162 of FDORA (Food and Drug Omnibus Reform Act) around “Bioresearch Monitoring Inspections” (BIMO), the boomerang effect from COVID-19, and what sponsors, CROs, and research sites need to be prepared for.

Amy Ripston (AR): The hot topic of the moment is FDORA, specifically giving the FDA greater authority and funding for Bioresearch Monitoring Inspections. Can you share your initial thoughts on this when it was released?

Edye Edens (EE): This certainly has raised a lot of questions, and to be frank, I am happy about its release. The fact of the matter is that FDORA isn’t introducing any new enforcements, but rather the FDA is being transparent about being more robust and thorough in their inspections – for what everyone should have been doing already.

AR: Can you elaborate? Why do you feel the FDA is bolstering their inspections?

EE: If you recall, when the COVID pandemic was declared, the FDA cleared the path for research to continue as long as patient safety came first. Decentralized clinical trial (DCT) models and technologies began to emerge and inspections were less frequent. Not that it has been a free-for-all by any means, but there have been so many new start-ups and new vendors. Without proactive measures, how are we confident that all of these are of highest quality?

The FDA has recognized the changes in clinical trials in recent years. They are warning the industry that inspections will return to pre-COVID levels, and they will ensure compliance among all stakeholders involved. At the end of the day, the FDA is good about being transparent with their expectations and encourages feedback, but they expect compliance during audits.

It’s almost a boomerang moment — we’ve come full circle from the pandemic. 

AR: Switching gears for a moment, do you see areas of regulatory risk when it comes to chain of custody of samples? Might this be a focus of BIMO inspections? 

EE: What sponsors, CROs, and sites may not realize is they are already contractually obligated to follow GCP standards around sample chain of custody. And, if they don’t ensure the sample chain of custody, in essence, it is a breach of contract, and that is huge.

My recommendation for each stakeholder is to check the Clinical Trial Agreement (CTA) for any areas that refer to liability, warranty, indemnification, compliance, and/or expectations for the conduct of the study. Specifically check any references to GCP, FDA, and sometimes even investigational product and biospecimens, etc. — it just depends on the type/purpose of the contract where it would be settled. 

Will this become a focus under BIMO? It’s hard to say, and we certainly don’t want to scare anyone, but it’s preventable so why shouldn’t we be proactive about it?

AR: Whose responsibility is it to ensure there is a traceable chain of custody for samples?

EE: This is a complicated question, mainly because of the way clinical trials are conducted. Sponsors are responsible for ensuring that the conduct of their clinical trials is compliant, and they need to show oversight. Ultimately, it is the sponsor’s data and if they don’t pay attention, they are putting their trials at risk.

But, of course, the sponsors aren’t the ones doing the work. They rely on their CROs and their clinical research sites to carry out the processes. Unfortunately that means a lot of the onus is placed on them, fair or not. What should happen is there is a joint responsibility between the sponsor, CRO, and site. 

AR: Earlier you mentioned the influx of DCT models and technology. How has this impacted the ability to ensure there is a chain of custody for samples?

EE: Traceability is becoming much more complicated as a result of DCT. Think about it this way: You might have a third-party vendor pick up a sample from a patient’s home and transport it to a testing facility. It definitely introduces more risk when the labs are not on-site. 

Additionally, what about the person who is delivering the sample? How much training are you giving them? How are you tracking it? They are part of that chain of custody for that biospecimen. When 1572s were rolled out, the FDA wasn’t thinking about DCT, but now they do expect everyone to figure it out.

AR: Given all of this, what advice would you give to sponsors, CROs, and sites in regards to the release of FDORA and sample chain of custody? How can they mitigate their regulatory risk?

EE: That they know where the skeletons are buried and it is time to be proactive in addressing them. Conduct a pre-evaluation and raise the red flag to leadership. Especially at the sponsor level, ensuring that everyone understands that FDORA was a heads up — a warning. They are giving you time to get your ducks in a row because after they do complete an audit, their expectations are high. 

I do worry that sponsors will push a lot of this down to the CROs and the sites, however, we are hearing a lot more noise from the clinical sites — that they have had enough. The power dynamic is starting to shift. Compliance should really be a joint responsibility for all parties — and I hope we get there. 

AR: Last question. Towards the beginning of our conversation you mentioned you were happy about FDORA and that it's necessary for advancing clinical trials. Can you elaborate on its benefits for patients?

EE: Oh, absolutely. Everything that we do on the compliance end benefits patients. It means drugs and devices will be vigorously tested. It means safety and efficacy claims will be pressure-tested from more angles. And since sample data is collected directly from patients, as proof of safety and efficacy, that will be a critical part of it. All of this together leads to better outcomes for patients.