According to the FDA document, Investigations Operations Manual (IOM),
the FORM FDA 483 INSPECTIONAL OBSERVATIONS is intended for use in
notifying the inspected establishment’s top management, in writing, of “...
significant objectionable conditions, relating to products and/or processes,
or other violations of the FD&C Act and related Acts which were observed
during the inspection.” This statement and other background information
can be found in section 5.2.3 Reports of Observations of the IOM. The FDA
goes on to point out that these reports of objectionable conditions are
made based on the judgment of the inspector. As with many government
inspections, the inspector has discretion in his or her interpretation of
what is “significant” and what is minor. Nevertheless, the issuance of
“written inspectional observations” is required by law when an inspector
finds a possible deviance from federal regulations.
Form 483s v. Warning Letters
It’s likely that the day comes when your firm receives a 483; naturally
you want to cooperate fully with the FDA in addressing the objectionable
conditions listed therein. One thing that you should be clear about is that
this is not a ‘Warning Letter’; it’s more like an offer to help you resolve issues
and improve your quality system. To be clear on the process: the FDA may
or may not issue a formal warning letter if you do not show that you have
addressed the observations within the 483 to the agency’s satisfaction.
However, it’s an important distinction to note that receiving a 483 does not
necessarily mean you are out of compliance.
10 steps to an effective 483 response
Your 483 response needs to accomplish these three things: establish credibility, demonstrate acknowledgement and
understanding of the observations and the associated requirements, and show commitment to corrective and preventive
actions. Below, are 10 steps that will help you achieve these objectives:
1. Get your response in on time or early if possible. The FDA wants to see the response within 15 days, so plan your review
and internal processes accordingly.
2. In the first paragraph of your response, demonstrate your understanding of and desire to comply with FDA regulations.
3. Respond individually to each item addressed on the form. Give a corrective action and time-frame for implementing.
4. Prioritize by first addressing the conditions that will most likely affect product quality.
5. Outline how and when each deficiency will be corrected.
6. Avoid talking about whose fault the issue is or how it came to be. For example, keep a positive tone and indicate how the
quality system will be improved.
7. Include any reference documents, such as purchase agreements for a new monitoring system or employment agreement
for a new quality manager.
8. Keep in mind that there is a formal process available for you to dispute the findings.
9. Be proactive in addressing the conditions. For example, address why the deficiencies were not detected internally and
what will be done to correct this condition.
10. Seek clarification with the inspector when you receive the 483 on the spot. Be sure you understand each objectionable
condition before the inspector leaves the site. Your firm may decide to seek out an industry expert if the matters seem
complex or if the issues are not able to be resolved by your own personnel.