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 (PDF download of her presentation here). In short, the response must:
- 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.
- Be Timely - 15 days, or even better, sooner.
- 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.
- 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.
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?
How do I avoid getting a Form FDA 483?
Don’t even give the FDA a chance to give you a Form FDA 483, right? All that headache of dealing with the aftermath! As they say, an ounce of prevention is better than a pound of all-day meetings and mad executives, right? FDAzilla’s research department just finished a report that addresses this exact topic. After reading through hundreds of 483s, talking with experts, former FDA investigators and high-ranking officials, and pharma execs, we boiled it down to 7 key strategies for avoiding Form FDA 483s. The report is available for purchase here.
And of course, another good way is to read up on what the FDA’s been issuing Form FDA 483s on recently. FDAzilla offers ~250 Form FDA 483s in the biotech and pharma industries. We charge $39 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.
FDAzilla 483s Resource Center:
- Form FDA 483s: 3 Types of Inspections
- What’s the big deal about these Form FDA 483?
- Who can see Form FDA 483s, and where do I get them?
- How to Respond to a Form FDA 483
- What have you learned from reading Form FDA 483 observations?
- Form FDA 483s listing, 2000 to present
- Form FDA 483s Store
- FDAzilla Report: Top Seven Strategies to Avoiding 483s