How to Respond to a Form FDA 483

How to Respond to a Form FDA 483

By | 2017-06-15T12:55:50+00:00 March 2nd, 2011|cGMP Quality Assurance and FDA 483s, FDA, FDA Inspections, Form FDA 483|

by Tony Chen

Previously, we covered Form FDA 483 basics.  Today, we talk about how to respond to them (and even better, how to avoid them).  There are basically 3 parts: the pre-response, the response itself, and the post-response.

Form FDA 483 | 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 is 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 Form 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 (e.g. “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 Form FDA 483 is a legal document and part of your company’s official history.

Form FDA 483 | The Official Response

In 2009, the FDA’s associate director for policy gave a presentation on how to do so effectively.  In short, the response must:

  1. Be Well-reasoned – look at root causes, look at systemic issues, and look at specific issues.  Explain things carefully and back it up with data/documentation.
  2. Be Timely – 15 days, or even better, sooner.
  3. Be Complete –  Address every single observation (not just all of them in general), articulate a plan of action for each, including time lines, metrics, monitoring systems.  This should include short-term as well as long-term corrective actions to prevent a recurrence.  Also state clearly whether you agree or disagree with each observation.
  4. Include a commitment/statement from senior leadership.  This serves just as another way to affirm the FDA that you’re serious.

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

Resource:  26-page presentation by Paraxel Consulting on how to respond to Form FDA 483s (PDF).

Form FDA 483 | The After-Response

This likely goes without saying, but once you submit the response, be strong in executing the plan.  At the end of the day, the Form FDA 483 and your response to it is just one aspect of a broader relationship that your firm has with the FDA.  Why not build credibility where ever possible?  Tell them what you’re going to do, and do it.

What else would you recommend in responding to Form FDA 483s?  What resources have you found useful?

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How do I avoid getting a Form FDA 483?

One good way is to read up on what the FDA’s been issuing Form FDA 483s on recently.   FDAzilla offers 7000+ Form FDA 483s in the biotech and pharma industries.  We charge $119 for individual Form FDA 483s, but also offer some special bundles.  Visit our Form FDA 483 store – you’ll get them instantly, anonymously, and more economically than asking for them from the FDA.

Learn more about how FDAzilla can help you achieve your quality and inspection preparation goals: get 483sInspector ProfilesEnforcement Analytics, and GMP Regulatory Intelligence.

FDAzilla 483s Resource Center:

  1. Form FDA 483s: 3 Types of Inspections
  2. What’s the big deal about these Form FDA 483?
  3. Who can see Form FDA 483s, and where do I get them?
  4. How to Respond to a Form FDA 483
  5. What have you learned from reading Form FDA 483 observations?
  6. Form FDA 483s listing, 2000 to present
  7. Form FDA 483s Store
  8. FDAzilla Report: Top Seven Strategies to Avoiding 483s

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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