Here's Your 483 — And Your Hug

By Dan Schell, Chief Editor, Clinical Leader

Over the past few weeks, I’ve been speaking with former FDA investigators to get their take on what clinical sites are doing right, what they’re doing wrong, and what they absolutely must be ready for. One of my favorite conversations was with Tracey Harris, who spent eight years with the FDA conducting inspections across sponsors, IRBs, and clinical sites as part of the Bioresearch Monitoring (BIMO) program.

Tracey also handled international pharmaceutical inspections and eventually moved to the private sector. But it was her time in BIMO that stuck with her. “I was really intrigued with how the patients go through the study,” she said. “Looking at how it’s all supposed to come together — that fascinated me more than anything on the pharma side.”

Tracey describes BIMO inspections as the most rewarding part of her FDA tenure, thanks in large part to the direct view they give into how clinical research operates at the patient level. And while she’s seen the full range of sponsor and site behavior, what stood out most were the operational realities at clinical sites — some of them impressive, others downright baffling.

“As an FDA investigator, we always felt like the bad guy,” she told me. “But my goal was never to make anyone feel small. It was to be fair, to help them understand what needed to be fixed.”

What Prepared Sites Do Differently

If your idea of inspection prep is dusting off a binder and printing out the protocol, you’re not ready. According to Tracey, readiness is about people, process, and presentation.

Start with the front room. “Have a host who can handle logistics and make the investigator feel welcome,” she said. That means a dedicated space with electronic access to documents, the ability to cast to a screen, and basic hospitality — coffee, water, and not looking like someone just set off a fire drill.

In the back room, organize your past couple of years of studies and keep that information ready to go. Prepare your SMEs well in advance. Let them review protocols or procedures before stepping in to answer questions. “Unprepared SMEs tend to ramble, and that’s when they say things they shouldn’t,” Tracey said. “That’s when FDA starts digging deeper.”

And no matter what, don’t fake confidence. “If I ask for an SME, don’t just shove them into the room. Let them know what I’m asking and give them time to prepare. People don’t always remember everything on the spot.”

She also emphasized the basics: clear documentation, especially around informed consent and blinding; privacy protections; and a documented subject recruitment process that maps clearly to your inclusion/exclusion criteria.

A Clinical Site Horror Story

When I asked Tracey for an example of what *not* to do, she didn’t hesitate.

“I went to a site where the records were in total disarray,” she said. “I couldn’t even tell who was in the study and who wasn’t. They’d hand me a patient record and then say, ‘Oh, that person wasn’t in the study.’ I’d ask, ‘Then why did you give this to me when I specifically asked for study subjects?’”

Study files were mixed in with general patient files, the consent process was unclear, and the site staff seemed confused about what she was even asking. The PI wasn’t present. Access to records wasn’t controlled. “It was a horrible site, to be honest. Completely unorganized.”

This wasn’t just a matter of bad filing — it raised questions about whether the trial had been conducted appropriately at all. “That inspection ended with a VAI rating,” she said, “and the sponsor was absolutely made aware.”

Answer Honestly — Just Not Too Much

When I asked about communication pitfalls, Tracey was quick to point out the danger of saying too much. “You don’t want to ramble, but you don’t want to mislead either,” she said. “Answer what’s being asked — truthfully and completely — but don’t volunteer extra information that wasn’t requested.”

That’s where unprepared SMEs can create unnecessary problems. “The minute someone starts going off-script, it sends a signal that they’re trying to cover something or just don’t know what they’re talking about. That’s when we start pulling on that thread.”

She stressed that this isn’t about being evasive. “If it’s bad and you’re asked, own it. Just don’t offer more than what was asked.”

The Basics Matter

One thing Tracey emphasized is that even small logistical details can shape how an inspection unfolds. Sites that stay calm and organized when FDA shows up — often unannounced — tend to make a much better impression than those that scramble.

Basic hospitality matters, too. Offering water or lunch isn't just polite; it's part of managing the rhythm of the day. But it should be done seamlessly, not as a way to stall. Internationally, it's common for lunch to be provided on-site — usually something simple like sandwiches or cafeteria fare — and that's perfectly acceptable. “You just can’t offer to take them out for some fancy steak dinner,” Tracey said.

Common Mistakes To Avoid

Tracey has seen the same issues pop up again and again during BIMO inspections. Some are fixable with better prep. Others signal deeper trouble. Here are the repeat offenders:

• Disorganized or missing documentation
• Inability to explain or demonstrate blinding procedures
• Unprepared SMEs giving inconsistent or off-topic answers
• Subject records not protected or improperly mixed with non-study data
• Overly technical or incomplete consent forms
• Subject recruitment processes not clearly documented or followed
• Lack of knowledge about applicable FDA regulations

Know The Regulations. Seriously.

The biggest gap she sees — and this was echoed by others I’ve spoken to — is sites not knowing the actual regulations they’re supposed to be following. “Some are just listening to the PI or the IRB,” she said. “But if you’re participating in a regulated study, you need to know the laws that govern it. It’s free on the FDA website. Print it. Read it.”

She gave the example of consent language. “It has to be simple. Layman’s terms. You can’t use doctor-speak or pressure people into participating. And if the protocol is off, but you follow it anyway without checking against the regulation? That’s still a mistake.”

Despite the seriousness of the job, Tracey made a point to treat people with kindness during inspections. She even told me about a long 483 she issued — followed by hugs. “I had one where we had real issues, but the team understood it, and we worked through it. When I left, it was all hugs and ‘Come back next time, Tracey.’” She laughed. “I still gave them the 483 — but I gave it with a smile.”