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 government 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 questions and comments, graciously accept the ticket, 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 a 483 from the FDA.
As an FDA regulated company, maybe 2020 and 2021 brought your organization relief from an FDA inspection. 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? Don’t panic yet! Let’s pause for bit more information.
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.
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 health. Also know that failure to correct deficiencies can lead to increased enforcement such as a Warning Letter or Consent Decree. 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, take a look at this issue and make the necessary corrections."
Now that you are calm, make sure you understand what the observations are about. You can’t make corrections unless you are clear on the underlying reasons for the observations in the 483.
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.
In your written 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 time-frames. You should expect the FDA to follow-up, so always do exactly what you said you would do at the timing that is listed in your response. The FDA does not look favorably upon missed commitments and deadlines.
It may be the case that your response contains evidence to counter the observations made in the 483. For instance, you have some information that the inspectors wanted but it 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 any and all systems, departments and processes that could be impacted by 483 observation and the written response. Check everything imaginable. It’s worth it.
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 as a result 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 on 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!
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.
If you don’t take the 483 seriously and do not respond, or your response is inadequate, you will face consequences. Essentially, it acts like an escalation system. And 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.
It’s important to note that you may also receive a Warning Letter if FDA officials have reviewed the 483 and made the conclusion that a serious violation may exist. This can happen whether or not you respond to the 483.
If you don’t respond to the Warning Letter, or your response is inadequate, the next step in the escalation process is a Consent Decree. A Consent Decree is a legal agreement that is reached between a company and the FDA and is overseen by a federal judge. And 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.
To avoid litigation, it’s a negotiated agreement that details the voluntary actions pledged by the company to remedy observations. 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. A Consent Decree may result in bankruptcy and shut your organization permanently.
Panic is never good. It leads to bad judgment and mistakes. When you receive a 483, 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 that are available for support.
We also recommend that you have ProPharma conduct a mock inspection after you’ve remediated the observations outlined in the 483. 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 compliant. Having this inspection completed communicates to the FDA that you’ve taken the 483 seriously and you’ve had a third party come in to help you remediate. 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. 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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