What is a 483? It is an FDA form used by inspectors to list the non-compliant items that they found during the course of a facility inspection. In the previous entry in this series, we discussed what to do when the inspectors arrive. Now, let’s discuss what to do when they leave.
The FDA form 483 is the result of industry’s requests that FDA investigators provide a list of findings upon inspection closure rather than waiting some time to hear from the Agency. The 483 is the vehicle for providing that information.
Responding to an FDA form 483
So, there you are, sitting across the table from the inspectors in a conference room at your facility. They have been there for a few days (or, in some cases, weeks). Typically, you’ve had daily meetings with the inspectors during their time at your facility. During those meetings, you have had a chance to discuss issues that came up during that day’s inspection. Some of those daily items may have been addressed (e.g. by updating SOPs, completing records, etc.), but now it is time for the final summary of FDA’s findings. The list that they give you on the 483 is the one that will go to the FDA District Office. Of course, the form says that the items listed may not be all of the items that are of concern, but what you receive represents the report that will move up the FDA food chain.
By this point, you have compiled a list of the items discussed during the daily meetings. You can use the cumulative list to identify the issues likely to be presented in the 483-inspection closeout session. With this draft in hand, you can plan your strategy for each item. Are you going to push back and present reasons why a certain issue does not represent non-compliance? Can you make your case with specific references to Federal regulations or FDA guidances? If not, then it may be time to rethink this strategy.
If you agree that the inspectors have identified a gap in your Quality system, what are your plans for addressing it? Who will be responsible? Who will speak to this at the closeout meeting? When do you expect your facility be in compliance in this area?
What to do during the inspection closeout meeting
Now you are in that closeout meeting going over the 483 with the inspectors. What do you do? What do you say? First things first: make absolutely sure that the most senior person available from your company/facility is sitting at the table during that closeout meeting with the inspectors. This is vitally important in demonstrating that your organization is taking the inspection findings seriously. That doesn’t mean that he or she should do all the talking, as it is likely that this senior individual will not have all the necessary information at his or her fingertips. The following is a sample exchange that may occur with the FDA inspector(s):
FDA Inspector: The next finding is related to the receipt of materials by your facility.
Your Head of Quality: Sue is our logistics representative; I’d like her to address this.
Sue, logistics representative: We recognize that our current system for recordkeeping in this area is inadequate. As we discussed with you on the day when this first came up, we plan to purchase industry standard software to address this issue going forward. I anticipate that this will be done and the installation and validation will be complete by the end of this year. The associated SOPs will be updated appropriately at that time.
Your CEO or Site Head: I will make sure that you have the resources necessary to make that happen.
Facilitating this type of conversation with the inspectors allows personnel with the appropriate expertise to respond to inspection findings while demonstrating that senior management is aligned and prepared to support necessary efforts to address the issue. This type of interaction also reduces the chance that the senior management members will speak about things which they may not be fully informed (which rarely ends well).
Next steps: What to do once the inspectors leave
The inspectors have packed up and left. Please understand that their work is not finished. They will be preparing a written report of their inspection, called an Establishment Inspection Report (EIR), which will be used by senior FDA officials to determine what action, if any, will be enforced upon your facility.
Now, you need to put everything that you said and promised in the closeout meeting into writing and submit it to the FDA District Office. How soon do you need to do this? Well, the sooner they receive it, the more likely it is to have an impact on the EIR. If you demonstrate that you have appropriately addressed a 483 finding, that should be noted in the EIR. For those findings which cannot be dealt with right away, you should include an action plan, with due dates, as well as a commitment to keep FDA informed of your progress. An example of an issue that cannot be dealt with right away would be a finding by the inspectors that your Quality system is severely lacking and ineffective.
The letter should be signed by the most senior person at your facility or, if appropriate, by someone senior to that individual at a multi-site company. It represents your firm’s commitments to address the issues that the inspectors have identified. In the case of a major finding like the example of an ineffective Quality system, you will want to identify in the letter any progress that has been made since the date of the inspection, and commit to update the Agency at regular intervals on the implementation of necessary changes. In the example of a deficient Quality system, this could include hiring an outside firm with recognized GXP expertise.
Finally, FDA will decide which category into which your facility falls:
- NAI, which stands for No Action Indicated, means that you passed the inspection. This is very good news.
- VAI, which stands for Voluntary Action Indicated, means that items of non-compliance are readily correctable and you just need to follow through on those corrections. This is also good news.
- OAI, which stands for Official Action Indicated, means that you can expect a Warning Letter from the FDA. This is very bad news. We’ll talk about Warning Letters in the next entry in this blog series.
At Pearl Pathways, we partner every day with companies to help them prepare for inspections and address issues which arise as a result of inspections. The next blog in this series will deal with what to do when you receive the dreaded Warning Letter. Check back to the Pearl Pathways blog soon to find out.
Read the other blogs in this series: