15 Days of Panic: You Received FDA Form 483 Warning Letter, Now What?

April 4, 2023

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This article has been updated since its original publication date.

Remember the last time you were pulled over by the police? Maybe you had a taillight out. Perhaps you were speeding. You may have believed that you had done nothing wrong. Regardless of the specific situation, you probably panicked a little. It's human nature to panic when the law enforcement (or in this case the US FDA) tells you that you've done something wrong.

Of course, the best thing to do is to remain calm throughout the process, respond politely to the officer's (inspector's) questions and comments, graciously accept the ticket, (483) then pay the ticket by the deadline or argue in court if you think you have been wronged. This is much like how to respond to 483 or warning letters from the FDA.

As an FDA regulated company, maybe 2021 and 2022 brought your organization relief from an FDA inspection due to COVID-19. Continuing the analogy above: are you ready for your inspection and related "ticket" from the FDA? Do you have adequate staffing to dedicate the required time and effort to a comprehensive 483 inspection response? Don't panic yet! Let's pause for a bit more information.

What is an FDA Form 483 Observation Letter?

The FDA issues a Form 483 at the conclusion of an FDA inspection when the investigators have observed conditions that, in their judgment, may constitute significant problems with your facility or equipment, the processes and controls you have in place, the products themselves, the practices of your employees, or your records.

The 483 is not a final Agency determination of whether any condition is in violation of the Food Drug and Cosmetic (FD&C) Act or any related regulations. The COVID-19 pandemic changed FDA's approach and timing for inspections. Some inspections are now done remotely, some have been deferred. Either way, the FD&C Act did not change. The FDA will catch up to their inspection plan. We'll cover more of this topic below.

Responding to a 483: Planning for Success

The first thing to do is to take a deep breath and do not panic. Don't even get defensive. It's not the end of the world or your project. Remember that it's not the job of the FDA to put you out of business. They are protecting the interests and well-being of the public's health. Also know that failure to correct deficiencies can lead to increased enforcement such as a Warning Letter or Consent Decree which are explained later. Great 483 responses and corrective action can prevent this increased enforcement.

Simply look at the 483 as an opportunity to learn from your mistakes and improve your processes by responding and correcting the observed conditions. It's just someone else looking at your processes from the outside and saying, "Hey, look at this issue and make the necessary corrections."

Now that you are calm, make sure you understand the observations. You can't make corrections unless you are clear on the underlying reasons for the observations in the 483.

Assessing your 483 Observations

Ask the right people within your organization what the FDA saw, heard, or read. Are the right protocols in place? Are they being followed? Has the FDA observed the issues detailed in the 483 before? Has the FDA raised any of those issues before and considered "Repeat Observations"? Answers to these questions will help you prepare your written response and take the necessary corrective action.

Responding to your 483

In your written 483 response, make it clear that you are taking the observations and your responsibility to correct the observed conditions seriously. Acknowledge all observations and describe the corrections being made. Make corrections immediately, if possible, otherwise set realistic timeframes. You should expect the FDA to follow-up, so always do exactly what you said you would do at the time that is listed in your response. The FDA does not look favorably upon missed commitments and deadlines.

It may be that your response contains sufficient evidence to counter the observations made in the 483. For instance, you have some information that the inspectors wanted but wasn't presented correctly. Perhaps there was a miscommunication, or they were given the wrong document. Simply explain the situation, and make sure the right document is available before the next inspection. The strategic approach should always include a comprehensive review of all systems, departments and processes that could be impacted by a 483 observation and the written response. Check everything imaginable. It's worth it.

Response Suggestions and FDA Priorities

Never mislead the FDA in your response. Don't make excuses related to short staffing due to COVID-19. Adequate staffing is required by the Code of Federal Regulations (CFR). Misleading is like giving the Agency the opportunity to pull that loose thread on your favorite sweater. Once they start pulling, the whole thing will unravel. Additionally, COVID-19 has created unique situations for the regulated industries supply chain. Do not blame lack of components like gowning materials or cleaning solutions because of non-compliance with current SOPs. Always remain compliant with SOPs even if it means slowing production.

A note about FDA priorities. The FDA now inspects facilities using a risk-based approach. The facilities that make life saving therapeutics, high volume, and have a low compliance record will likely end up at the top of the list. Those facilities with low volume, non-life saving therapeutics and high compliance levels will fall to the lower part of the FDA list. Example: if your organization makes millions of IV bags a year and has an active Warning Letter – you are at the top of the list. Be prepared!

The Consequences of Not Responding to the 483 Letter

When you receive an FDA Form 483, you must respond within 15 business days. However, to make sure that your response is timely, it's best to respond within 15 calendar days. That shows the Agency that you are being proactive and that you are taking the observations seriously.

483 Warning Letter

If you don't take the 483 seriously and either fail to respond provide an inadequate response, you will face consequences. Essentially, there is an escalation. The next step is a Warning Letter. This letter is a formal notification that allows for voluntary and prompt corrective action relating to specific observations. Your written response to the warning letter must communicate a revised plan of action. This plan is your last chance to avoid further escalation of consequences.

You may also receive a warning letter if FDA officials review the 483 and conclude that a serious violation may exist. This can happen whether you respond to the 483 observation letter but should never prevent you from providing an adequate response

Consent Decree

If you don't respond to the Warning Letter, or your response is inadequate, the next step in the escalation process can be a consent decree. A Consent Decree is a legal agreement reached between a company and the FDA and overseen by a federal judge. To make it even worse, the FDA can "skip steps". If your organization is significantly out of compliance, the FDA can go directly from 483 to Consent Decree.

Essentially, the consent decree serves as a negotiated agreement detailing your company's pledged voluntary actions to avoid litigation. Consent decrees commit companies to perform corrective action in a timely manner. In laymen's terms, it is a court order that something must be done. Well-planned and detail oriented 483 responses can prevent such significant impacts to your organization.

Further, consent decrees empower the FDA to impose fines for not completing the corrective actions according to the agreed upon timeline. The Agency may also halt production, which may result in bankruptcy and shut your organization permanently.

ProPharma can help with FDA Form 483 Letters

Panic is never good. It leads to bad judgment and mistakes. When you receive a 483 letter, you have two options: panic or plan for success. We suggest you contact us immediately so that we can help you plan for success. We'll work with you to put together an appropriate response, structure it in a logical format, and submit it before the deadline. We have a host of seasoned, regulated industry professionals who can support you through this process.

We also recommend that you have ProPharma conduct a mock inspection after you've remediated the observations outlined in the 483 letter. This inspection will give you clear feedback as to whether what you told the FDA you would do has been done and that everything observed is now compliant. Having this inspection completed communicates to the FDA that you've taken the Form 483 seriously and had a third-party assist in the remediation. Worried that your organization has lost its "edge"? ProPharma can also provide FDA Inspection Readiness training.

A 483 is nothing to panic over. You just need to have the right partner to calmly work through what needs to be done. Contact us today and, together, we can work to successfully resolve a Form 483 letter.

Are you reading this after you submitted your 483 to FDA and have corrective action to take? We can help with that as well. Contact us for immediate and robust support.

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