What practical tips do you have in avoiding and responding to Form FDA 483s?
- Inspect the FDA as well. You can see 15 years of FDA statistics condensed into a single infographic.
- Get a sense of what constitutes as big red flags for the FDA. Although we focus on 483s, understanding the FDA’s trends in warning letters and their timing can help you prioritize as you prepare and clean up shop.
- Practice inspection readiness every day. Run “mock” audits regularly and review findings so that teams are calm and confident during actual inspections. (Source: anonymous, 3/11)
- Obtain 483s from your industry that are readily available from the FDA or other sources (such as this list we compiled of 483s based on data integrity issues). This will give you a flavor of what they’re emphasizing (Source: B.B. @ food industry, 3/11) If you have a few days advance warning of who your inspector is, you can always do a search on previous 483s issued by your inspector & purchase them here.
- Finally, not all inspectors are the same. We show you how you can “Facebook” inspectors here.
During the Inspection
- On the day of the actual inspection, only answer the question that the FDA is actually asking. One pharma company trained their people this way: If the FDA asks you, “do you know what time it is?” You should say, “yes.” (Source: anonymous, 2/11)
- Have senior people in the organization be the point person to the FDA inspectors. You don’t need an entire team following them around all day. Choose people who are calm and confident. Utilize other team members in preparing, assembling requested documentation, CDs, etc.
- A backroom is essential during FDA inspections. Ideally, this room should be projecting the chat from the inspection room. Experts from across the product lines and Quality Assurance / Regulatory Assurance should be in the back room. They should be ready to provide documentation to support the inspection at a moment’s notice. (Source: David @ big device company, 3/11)
- Utilize the close-out meeting to clarify any items that remain unclear. This helps you understand exactly where the inspector’s head is out, and honestly, sometimes you’ll uncover some misunderstandings and lead to less observations. Do NOT use this meeting to defend your operation. If you’ve already taken some corrective action during the inspection, it may be wise to ascertain whether the inspectors deem these actions sufficient. (M.R. @ international pharma company, 3/11)
- The exit interview is VERY important in establishing the intention of Senior management to perform corrective action and CAN minimize further action. The FDA Investigator has a great deal of input as to how the Compliance Branch will classify an inspection. If senior management appears flippant and unwavering (yes this STILL happens!) – expect the District to at least attempt to upgrade a 483, to a warning letter. (Holly Scott, Biologics Consulting Group, 4/11)
- Once the inspection is over, the best way to avoid Form FDA 483s is to respond to the current observations as specifically, comprehensively, and swiftly as possible. The FDA is understandably not sympathetic to companies with repeat observations.
- Just because the inspector wrote the observation doesn’t mean that you can’t dispute it. You can disagree on the facts in which the observations were made on, or you can disagree on whether the observation actually worthy to be written up.
- Heard: “We know within 30 seconds of scanning your response if you ‘get it’ or not.” – Tim Ulatowski, Director, Office of Compliance
- A lot has been written on how to craft an exceptional written 483s. Check out some of the presentations on our home page as well as the 10.5 tips from this article from Veriteq.
- The main thing I learned is that quality is 100% dependent on the organizational culture. People from all departments have to have a sense of shared ownership in quality – i.e. it’s not just the quality department’s job to ensure quality, though it’s their heads that roll if something does happen (Source: anonymous @ big biotech)
- Speaking of a “culture of quality,” one of the best places to read up on that is the QA Pharm, the cut-to-the-chase blog of an anonymous quality executive who’s obviously been around the block.
Do you have a good resource to add to this list? Please submit by contacting us. We’ll credit you as the source if you’d like.
by Tony Chen