FDA Form 483 requires a written response in which you must make it clear that you are taking the observations, and your responsibility to correct the observed conditions, seriously. It is essential that you make corrections immediately or set a realistic time-frame for corrections. The Agency will follow-up, so be sure to do exactly what you said you would do in your response to the 483.
Not responding to a Form 483, or submitting an inadequate response, can lead to increased enforcement actions like a Warning Letter or Consent Decree. These actions include giving the opportunity to voluntarily correct and prevent violations, enforcing involuntary corrective action, removing violative products from the market, and punishing offenders. The type of enforcement action the Agency uses depends on the nature of the violation and whether the violation has been remedied to the Agency’s satisfaction. An accurate and robust 483 response is essential to preventing further enforcement from FDA.
There are 4 common pitfalls in 483 responses that ProPharma Group assists clients with frequently.
The first is inexperience with the process. If your site is being inspected for the first time, such as a Pre-Approval Inspection (PAI), you don’t want FDA to be your first inspection. FDA are sure to discover issues that could have been corrected if you found them first. For this reason, it is critical to conduct internal audits and third-party audits prior to FDA inspections. Your objective is to shine a light on compliance issues and fix them before the Agency comes in and has the chance to find them. Inexperience is not easy to overcome, but the third-party GMP experts at ProPharma Group can support you and your team.
#2: CAPA Delivery
The second common pitfall is over or under promising corrective actions. Many organizations struggle with this. Although there is only a 15-day window to submit responses to FDA following the inspection, it must be a comprehensive, accurate document. Predicting the future of your CAPA is difficult, but it has to be done. As an organization, you must deliver your corrective actions with precision and accuracy. If the FDA is unhappy with your response, they will let you know. Does your organization have a capacity to handle increased enforcement action like a Warning Letter?
#3: Missed Deadlines
The third common pitfall is missed deadlines. As mentioned previously, the CAPAs must be accurate and comprehensive. If your organization sees that it is going to miss a deadline that was part of the formal 483 response, you need to notify FDA. This is an uncomfortable process for two reasons. First, it admits a failure to deliver your commitments to protect the public health. Second, it alerts the FDA that your organization is struggling to deliver what they may see as a simple correction. Do not let this situation occur. All resources necessary should be pushing the 483 CAPAs to completion – on time or early!
#4: Limited Scope
The last pitfall ProPharma Group sees is a CAPA that has a very narrow scope. Let’s say the FDA cites your firm for an SOP that was not followed. Your CAPA states that you will retrain all relevant personnel on that SOP. Red flag! Are you certain that all SOPs are being followed as written? Have you conducted a comprehensive audit of all critical processes to ensure compliance? You should. We’ve seen it many times. On the next inspection, the FDA will find the same problem in a different area. The citation will read like this: This is a repeat observation from the last FDA inspection conducted <date>. And yes, it’s written in bold to emphasize the point: your organization did not have a broad enough scope in the original CAPA.
If you have questions or need support responding to a 483, contact ProPharma Group to ensure you have the expertise and experience needed for a successful response and remediation.
Check back in for my next blog where I will cover recent changes to the Regulated Industry in response to COVID-19, how FDA has changed as well, and what your organization can do to succeed in our new regulatory environment.
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