FDA update June 7, 2012

FDA’s new policy for 483 Responses –

Be aware what is needed to prevent a Warning Letter

If you recently have had an FDA inspection or if you are presently involved in one, or you may have on in the near future, you should be aware of the present FDA policy on how to get your response to the 483 into the FDA. Your response is the only way to possibly avoid the issuance of a Warning Letter or to at least have your response made part of the W/L.

If you thought that the response to the 483 could be sent into the FDA within 15 days on your action plan to address the observations, this is not good enough. The FDA is not only expecting that you get your response into them within 15 days, but they are expecting that your corrective actions have been completely addressed and implemented. Sounds impossible. Well for most companies it is.

This goes back to August 2009  when the then new FDA commissioner, Dr. Harriet Hamburg, made a speech outlining the “new” FDA initiatives. There were going to be 6 changes, one of these changes directly addressed how the FDA was going to deal with inspections were out of compliance.

“Below are the six changes that she mentions that can be expected in the FDA enforcement practices. These new practices are being implemented to Protect the American public. As you will see, these initiatives will put a lot of pressure on the FDA regulated industries. Therefore, it is critically important to assure the industry fully understands the FDA objectives and its expectations for industry cGMP compliance. It would appear that making a miscalculation in this area could result in the issuance of a Warning Letter, expedited FDA follow up and if problems still exist, additional swift regulatory actions. How this will be enforced Region to Region will be interesting to observe as the FDA moves to a high octane regulatory agency looking to “enforce” the regulations fast and furious.

The six new initiatives are:

“First, the FDA will set post-inspection deadlines. When the FDA finds that a firm is significantly out of compliance, we expect a prompt response to our findings. Once the FDA provides inspection findings identifying a serious problem, the firm will generally have no more than fifteen working days in which to respond before the FDA moves ahead with a warning letter or enforcement action. This will help FDA issue warning letters on a timely basis and facilitate prompt corrective action”.

(see FDA update August 12, 2009)

These changes to how the FDA is dealing with 483 responses and the issuance of Warning Letters was just observed over the last few months. In one case the FDA stated that they received a response to a 483 within the 15 days but the follow up responses outlining the CAPAs that we promised in the 483 response were not received within the 15 days and were not reviewed. That warning letter was issued 4 months after the 483. The last response to the 483 was supplied within 45 days of the 483. Not sure where consumer protection comes in with the issuance of the Warning Letter.

We recently saw a Warning Letter where the New York District referred to the response to the 483 in the warning letter as follows:

“Your firm's response to the Form FDA 483 (FDA 483) was received by New York District via email in an unsigned document after the close of business on the fifteenth business day after the FDA 483 was issued. The email did not provide attachments related to your response. However, the email indicated a signed response as well as attachments were available for the FDA by logging onto a Siemens File Exchange. The District did not and does not plan to logon to your firm's File Exchange to obtain responses or other information. In addition, the email indicated a hardcopy response was being sent to the District Office. The District received your hard copy response on January 23, 2012.”

So, as you can see the new FDA policy on 483 responses is one that is not set up to work with industry trying to comply but one that is to show how many warning letters can be issued. Be aware that the FDA at the present time is not working with the industry. You need to understand that the response to the 483 not only has to be addressed in the 15 days but you must have the CAPA completed and implemented in that period. That information along with the full documentation must be into the FDA to prevent any possibility of the issuance of that warning letter.

If you are presently involved with an FDA inspection or trying to respond to a 483 or Warning Letter, please feel free to contact us to discuss your options.

If you would like to discuss the FDA regulatory strategy and what it can mean to you please contact us at info@mdiconsultants.com and ref: FDA “483 response”.