The Clock Is Ticking – Responding to FDA 483 in 15 Days

April 26th, 2013 // 3:00 am @ jmpickett

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When you respond to an FDA 483 for cGMP violations, you need to be sure that your response letter addresses each specific violation. Many companies will address the individual FDA complaints, but they never actually get down to a real solution to the problems.

Of course, developing a strong response letter that addresses each inspectional observation in its entirety has gotten more challenging. Now the agency is putting more pressure on all drug manufacturers to answer within 15 workdays after an inspection closes out. The clock is ticking!

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If you do not answer the 483 cGMP violations in that time frame, FDA will not even open your response! This means that you can spend thousands of dollars on FDA consultants for naught, if you don’t get that letter in within 15 days.

That is why for many companies, those 15 days are a panic. It is, in our view a good idea to think of those 15 days as calendar days, not business days, as FDA views it. There are several good reasons to view the 15 days as calendar days:

Everyone in your company will understand that the 483 response is the most important item. A bad response will assure tougher regulatory actions, including a possible warning letter. This will cause the value of the company to decline and sales and stock prices to suffer.
If you get your FDA 483 response done quickly and efficiently, you may end up with a few days to think it over. You can have some time to tweak or clarify some of the responses.
By assuring that you get the FDA 483 response done in 15 calendar days, you will have ample time to look the response over. Look, a lot is riding on that response letter. Do not glance it over in 30 seconds before mailing it.

Only Include Realistic Time Frames in 483 Response

Do not overpromise to FDA on when a cGMP violation can be fixed. Be realistic. If you over promise and FDA comes back and there are still problems, you are going to get written up again in another 483, and a second write up for the same violations can lead to a warning letter.

It also is a good idea to not just give a reasonable time frame, but also to show that you are making progress in your quality operations as well. Many FDA correspondence letters often say that the 15 day response was not good enough. One big reason is that the pharmaceutical company says they need four months to fix a problem. But they do not tell FDA why it will take that long and what the due dates and milestones are in that four months.

You want to say in your response: This is our remediation plan, these are the items in that plan we are going to do, these are the milestones, and these are the final target dates for completing each part of the remediation plan.

FDA should be able to take your response, and come back to your plant in 3 months, 9 months or in a year and know just where you are on solving the 483 problems. If you do not have that type of detail in your response letter, you should get a consultant to help you.

Always remember that after you get that 483, the 15 day clock starts the second the auditor leaves your plant. One good idea is to have a checklist or an observation closure list or matrix in your SOP for handling inspections. You should match the FDA observation with the symptom and then to the person in your company who is the point person for fixing that problem, and then match this to the records generated that occurred when you closed that compliance gap.

Your Post-483 Inspection To Do List

You should first look at all the 483 observations that need to be fixed. If the FDAer noted that your change control documents were not adequate because they did not have signatures, missing signatures is probably a symptom of a larger issue. The sigs are not there for some reason. It might be because your change control processes are too complex and you need to make the procedures more efficient. Or your training may be not good enough. The idea is to take a step back and figure out what the root of the problem is. FDA expects you to do that.

15 days can be tight to do this, so you want to have a very simplified process to do it. One way is to use a matrix that shows observation closures. You want to list the documents that will prove the fix. So it is simple to see if you are just focusing on the symptom of the 483 or are dealing with the bigger breakdown of quality control. If you are focusing on a symptom, you will have just a small amount of documentation, such as new SOP. But if you are tackling the bigger problem, you will have a lot of documents, including a new change control SOP, a new process map, more training manuals, a new form and so forth.

For more information about 15 day 483 response tips, check out our upcoming Webinar on FDA Tips and Tricks to Survive Your Next Inspection.

H/T: Cerulean Associates

The Clock Is Ticking – Responding to FDA 483 in 15 Days