Even before any FDA inspection, be sure the firm is already proactively trained about the proper way to respond to an FDA 483. Consider supplementing this with an SOP explaining what to do when the time comes. This way, the firm isn’t scrambling and doesn’t misstep at that critical moment when the FDA 483 is presented.

During the opening meeting of the FDA inspection, request that the investigator inform the firm in real time if objectionable conditions were observed and are being noted by the investigator. It is common for the investigator to do so already; but it is still advisable to make this request anyway.

During the FDA inspection, request daily wrap-up discussions so as to facilitate preemptive dialogue between the agency and the firm regarding any questions that either party has about objectionable conditions that have been observed. A goal of this is that there be no surprises or new information presented at the closing meeting when the FDA 483 is officially issued.

At the closeout meeting when the FDA 483 is officially presented:

Politely and thankfully and respectfully acknowledge receipt. Have each FDA 483 Observation annotated to establish the firm’s cooperative and interactive stance. FDA’s standard operating procedure is to invite the firm into the annotation process; however, I have seen FDA investigators fail to follow their own SOP on multiple occasions before. Thus, be sure the firm takes the lead if needed to assure that the Observations are annotated. Some typical annotations (not comprehensive) are “Corrected and verified”, “Promised to correct” or, less commonly, and to be avoided if possible, yet definitely needed for an Observation with which the firm isn’t yet in agreement, “Under consideration”. Express the firm’s intent to provide FDA with a written response to the FDA 483 within 15 business days. By procedure, FDA looks for and expects this as part of deciding whether further FDA escalation is needed. Thank the investigator again for the inspection. Closeout.

After the inspection:

Prepare and submit to FDA a comprehensive written initial response to the FDA 483. Specifically,

Be sure the response is officially from Management with Executive Responsibility (MER), preferably the top officer (CEO/President) [though the response is actually generally ghost-written by the firm’s qualified FDA regulatory expert(s)]. MER needs to reiterate the firm’s intent to cooperate, to protect public health, and that it takes FDA’s Observations seriously. Address each FDA 483 Observation in itemized fashion. Specifically,

Open and cite a CAPA for each one including appropriate background or clarifying explanation. Process each CAPA at least through the risk assessment, root cause analysis, and planning of the required correction(s) and corrective action(s). Include a copy of the CAPA; don’t make the mistake of making promises or advising FDA about actions taken (e.g., CAPAs) without providing the corresponding objective evidence/proof. Include the firm’s intended closure date for each CAPA. Be realistic about the intended closure date; don’t rush things in a fit of good intentions to show commitment only to wind up having made promises that the firm can’t fulfill. FDA wants genuine proper action, and this oftentimes takes time; sometimes even a year for larger FDA 483s. For any corrections or corrective actions already taken, include evidence as mentioned above.

In cases where all of the CAPAs can’t be fully and properly processed and closed within the 15-business-day window, then provide FDA a promise of progress reports. Submit the response to FDA at the directed office and email address [e.g., Office of Regulatory Affairs’ Office of Medical Device and Radiological Health Operations (OMDRHO) Division 3 – West at [email protected]]. FDA will generally give a handout explaining which office is assigned for the firm’s geographical location.

Prepare and submit the promised progress reports, again to the same office as before. Do this until you receive a “VAI Letter”.

The process starts all over again.