How to Respond to FDA 483s

What does it even mean to officially respond to a 483 and, better yet, how can a 483 be avoided altogether? The answer is basically split into 3 parts:

  1. The Pre-Response
  2. The Response Itself
  3. The Post-Response

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1. The Pre-Response

You can talk directly with the inspectors during and after the inspection to clarify points and understand their reasoning better. Inspectors are, in fact, directed to discuss all observations with management as they are observed (or at least on a daily basis) in order to minimize any surprises down the line.

You don’t have to agree with every observation. Or, even if you agree with the observation itself and the facts used to get there, you might disagree that the observation represents an “objectionable condition or practice” (this is where you have to know the law/code – the Federal Food, Drug, and Cosmetic Act Section 704(b) is all on factory inspections). Remember, the FDA can issue FDA 483s under this authority:

The observations of objectionable conditions and practices listed on the front of this form are reported:

  1. Pursuant to Section 704(b) of the FFD&C Act
  2. To assist firms inspected in complying with the Acts and regulations enforced by the FDA

Of course, don’t make excuses (i.e., “Come on, we’re just a struggling company trying to survive. Just cut us a break, k?”). If you disagree with the facts of the observations or that the observations are objectionable, back up your claims with data, literature references, code references, and other scientifically sound justifications.

If you do feel that there is an error in the 483, it is worth trying to correct it. After all, the FDA 483 is a legal document and part of your company’s official history.

2. The Official Response

In short, the response must:

  1. Take a systemic and global approach. Don’t simply address the 1 or 2 examples in the observation that the FDA found problematic. Look broadly. Also, look across all company sites. FDA does not want to find the same problem at each of the company sites they inspect. That alone may be cause for additional actions.
  2. Be well-reasoned. Identify root causes, consider systemic issues, and look at specific issues. Explain things carefully and back it up by submitting data/documentation including revised SOPs, protocols, or other documented evidence. Many warning letters identify the failure to submit documentation and evidence as part of the 483 response.
  3. Be timely. Submit the response within 15 business days after the close of inspection if you want your responses to be considered by FDA when they decide whether to take additional enforcement action such as a warning letter. If you respond later than 15 business days, FDA is not required to consider your response as they decide on additional enforcement action.
  4. Be complete. Address every single observation (not just all of them in general), articulate a plan of action for each (including timelines, metrics, and monitoring systems). This should include short-term as well as long-term corrective actions to prevent a recurrence.
  5. Include a commitment/statement from senior leadership.  

Also keep in mind that your response will be read by multiple people at the FDA, some of whom are not as technically familiar with your company or your technologies. At the very least, the investigator, his/her supervisor, a compliance officer at the district office, and maybe other FDA headquarters personnel will review your response.

3. The Post-Response

This likely goes without saying, but once you submit the response, be diligent in executing the plan. At the end of the day, the FDA 483 and your response to it is just one aspect of a broader relationship that your firm has with the FDA. It represents your commitment to the FDA, and rest assured that the FDA takes those commitments seriously. Tell them what you’re going to do and do it. If an unanticipated delay occurs in remediation, it is reasonable to communicate that delay to the FDA.

How do I avoid getting an FDA 483 to begin with?

We have over 11,000 Form FDA 483s in our database that are keyword tagged, searchable, cross-referenced for easy comparison, and easy to copy/paste/print.

With a subscription to our Enforcement Analytics platform, not only do you have access to all of the 483s in our database, but you also have the power to run macro trend reports, monitor your CMOs/suppliers, investigate your inspector, and more with just a few clicks.

Or, if you prefer, you can also purchase individual 483s for $119 in our document store to get the reports you need instantly, anonymously, and economically.

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*Updated in 2018 | Originally posted in 2011.

About the Author

Paul Brooks

Tony Chen is Chairman and Co-Founder of FDAzilla, and served as Founding CEO from 2010 to 2017.

About the Author

Barbara W. Unger

Barbara W. Unger formed Unger Consulting, Inc. in December 2014 to provide GMP Quality consulting services to the pharmaceutical and biopharmaceutical industry. At Amgen, she led the segment of the Corporate GMP Audit group at Amgen focused on API manufacturers, Quality Systems and Computers. She developed, implemented and maintained the GMP Regulatory Intelligence program for 8 years at Amgen Inc. This included surveillance, analysis and communication of GMP related legislation, regulations, guidance and industry compliance enforcement trends. This was an essential service and tool within the Corporate Audit function.

Unger Consulting Inc. | www.ungerconsulting.net | 805.217.9360

10 Comments

  1. anonymous @ big biotech March 2, 2011 at 2:37 pm - Reply

    Good article on Form FDA 483s. From my experience in preparing our sites, this is what I’d recommend:

    Practice inspection readiness every day. Companies should know their shortcoming and areas where they are working to improve. None of us is perfect but understanding strengths and areas of vulnerability can be used to focus resources and action. Part of daily inspection readiness is also ensuring that facility housekeeping and maintenance are flawless and this includes areas outside of the manufacturing plant. You never get a second chance for a first impression.

  2. anon March 2, 2011 at 3:21 pm - Reply

    Be careful of committing to CAPAs just for show.

    Remember, the FDA expects commitments made in 483 responses – no matter how nonsensical – to be executed.

  3. […] How to Respond to a Form FDA 483 (FDAzilla Blog).  This is a complicated question and has many complicated answers.  But the short answer is as specifically, comprehensively, quickly, and logically as possible for every single observation.  Attack each one with passion.  Explain to the FDA how the observations will be addressed, when, and how you’ll monitor it on an on-going basis.  Don’t be that company that gets repeat violations. […]

  4. […] How to Respond to a Form FDA 483.  The short answer is as comprehensively, quickly, and logically as possible for every single observation.  Attack each one with passion.  Explain to the FDA what you’re going to do to address the issues, how you’re doing to do it, when you’re going to do it, and how you know you’ve done it.  Don’t be that company that gets repeat violations. […]

  5. Susan April 14, 2011 at 2:38 pm - Reply

    Question – after submitting a response to a form 483, can we expect some sort of closure/response from the FDA? This is assuming there will not be a warning letter.

    thanks –

  6. […] How to Respond to a Form FDA 483 […]

  7. […] How to Respond to a Form FDA 483 […]

  8. […] What do we do after the FDA completes the inspection?  If the FDA investigator observes anything that could be out of place, they notate it in the FDA 483 report. These reports are simply inspectional observations, and do not represent a final agency determination.  If you do receive an FDA 483, you should respond swiftly and comprehensively. For more on how to respond to an FDA 483, visit this article from FDAzilla. […]

  9. […] What do we do after the FDA completes the inspection?  If the FDA investigator observes anything that could be out of place, they notate it in the FDA 483 report. These reports are simply inspectional observations, and do not represent a final agency determination.  If you do receive an FDA 483, you should respond swiftly and comprehensively. For more on how to respond to an FDA 483, visit this article from FDAzilla. […]

  10. […] How to Respond to a Form FDA 483 […]

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