Keep Calm and Carry On: How to Survive an FDA Inspection

Posted February 21st, 2019 by Aoife Brennan, in FDA, From The Trenches

This blog was written by Aoife Brennan, CEO of Synlogic, as part of the From The Trenches feature of LifeSciVC.

It was apparently random, although I secretly suspect it was karmic punishment for my lack of imagination in writing the 2019 quality goal. It has been ‘Maintain the quality management system and documentation in inspection-ready form’ for the past 3 years. While we take quality and regulation seriously, our assumption, like that of many early-phase companies, had been that an actual FDA inspection was several years off. I had previously been involved in pre-approval inspections and the questions regarding early studies were always the most difficult to piece together; the team who ran the study had moved on or the asset was in-licenced. For this reason, we had invested in making sure we had a good filing structure from the start and were maintaining the appropriate documentation. It now appeared that these efforts would be put to the test.

The development organization at Synlogic was about 2.5 years old at the time of the inspection. In my prior role as CMO, I had led the creation of a basic set of SOPs, mainly focusing on vendor oversight. We had maintained our training records and documents in a fire-proof locked cabinet. Keeping it simple helped us get good compliance with training. This was the quality management system 1.0 that was in place for the initial trials we conducted. When the inspection occurred, we were mid-way through the process of moving to a cloud-based document management and training solution and of assessing which additional SOPs we needed. While our future plans were not officially taken into consideration, it certainly helped for the investigator to know that we were attempting to stay ahead of the needs of the growing organization.

We got a call the Monday after JP Morgan, during the government shutdown, to indicate that an FDA investigator would be on-site in two days. Our head of Regulatory sent me an SMS, which was followed by an email from our head of Quality with a warning that the SMS was not fake news. We gathered the team and quickly realized that very few had participated in inspection training or a real inspection in the past. Luckily, our head of Quality had plenty of notches on his belt and developed an action plan that included establishing a back room/front room operation with a system for tracking document requests. We created a dedicated Slack channel to keep everyone on the team informed and put external vendors who might get called on notice. Conscious of the growing nervous energy, I framed the inspection as an opportunity to review our systems and implement changes if needed. It felt like my old job as a physician, trying to convince a nervous patient that a colonoscopy was actually fun as you could see your insides on the TV screen.

At the given time, the investigator arrived on site. Despite her very personable demeanor, the US public health services uniform and official looking ID seemed to push team-members closer to the edge. My prior inspection experience was from the era of paper-based trial master files. I had not anticipated, but it made perfect sense, that most documents for this inspection would be reviewed electronically. Lots of thumb drives were needed. The investigator outlined the anatomy of the inspection and, after a round of intros and the company presentation, we got going. Nerves seemed to abate once the rhythm of document requests was established. The focus of the inspection was to be a single-site, healthy volunteer Phase 1 trial. Despite what seemed like limited scope, over the course of five days on-site 78 requests were made, eight presentations given by various team members and 456 files were provided to the investigator.

The team did a nice job interacting with the investigator; they were open and non-defensive as her questions were discussed and prompt in providing the requested documentation. The investigator was gracious enough to point out areas where process improvements should be considered as we move into more complex studies, but was happy with our documentation and oversight of the trial. While there was a good outcome and lots of learning, there was an audible sigh of relief when the investigator said goodbye on the last day.

We now realize that an FDA inspection really can occur at any time and have learned that the team can drop everything and come together to get through an unexpected and unplanned chunk of work. Being ‘inspection ready’ will continue to be our quality goal and I suspect that now it has more meaning for everyone. Managing emotions and team dynamics during a stressful period is as important as the preparation. As with most other situations in life, when the work is done and the FDA arrives, the key is to keep calm.

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