FDA’s Office of Scientific Investigations (OSI) conducted 430 clinical investigator-related inspections in 2015, and while just six resulted in 483s (compared to 16 in 2014), it’s not something industry should take lightly. In fact, while responses are optional, the wise strategy is to respond as soon as possible, advised David Burrow, Acting Deputy Director at the agency.
First, it’s helpful to know what FDA looks for during an inspection, he told attendees of ACRP’s 2016 Meeting & Expo today. Agency focus can essentially be distilled down to ten areas:
- Verify primary efficacy and safety data.
- Source of subjects; did subjects exist?
- Did they meet inclusion/exclusion criteria?
- Was IRB Review obtained? Consent?
- Adherence to protocol?
- Verify primary efficacy measurement.
- Adverse events?
- Adequate safety data, e.g. Labs, EKG, etc.
- Drug accountability? Blinding of data?
- Was informed consent properly documented, including substance and process?
Burrow emphasized that, while there is no regulatory requirement to respond to a 483, a well-reasoned, complete and timely response is “in your best interest.” Still, there’s a pretty strong motive. “A complete and timely response could mitigate an FDA compliance decision,” he said. He cited three other important motivations. It:
- Demonstrates acknowledgement and understanding of the FDA observations.
- Demonstrates commitment to correcting the observations.
- Establishes credibility with the agency.
Burrow offered nine 483 response suggestions:
- Include a commitment from senior leadership.
- Address each observation separately.
- Note whether you agree or disagree. Bonus tip: Prove it.
- Provide both corrective and preventative actions.
- Provide both completed and planned actions.
- Provide a method of verification or monitoring the effectiveness of the actions.
- Submit documentation of training, SOPs, and other records.
- Submit the response within 15 working days.