June 6, 2019
You can expect several FDA audits throughout your drug development program The Agency’s goal is to protect the public from unsafe products, and one of the best ways to accomplish that goal is by visiting facilities to determine whether they are compliant with FDA regulations.
You never want the FDA to conduct the first inspection because they 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.
An FDA inspection is an official examination of a facility and its quality systems to determine compliance with applicable regulations. The Agency conducts four types of inspections for which your organization must be prepared: a pre-approval inspection, a routine inspection, compliance follow-up inspections and a for-cause inspection.
The first type of inspection is a pre-approval inspection, which is conducted after a Sponsor submits a marketing application to the FDA. The objective is to determine whether the methods, facilities, and controls are found to be adequate to ensure and preserve the drug’s identity, strength, quality, and purity.
The second type of inspection is a routine inspection. The Agency might conduct this type of inspection every two or three years during the drug development process.
The third type of inspection is a compliance follow-up inspection. The Agency will conduct an this type of inspection to verify that there has been adequate corrective actions implemented of previous violations, to document continuing violations, or to support future regulatory action.
The forth type of inspection is a for-cause inspection. The Agency conducts this type of inspection to investigate a specific problem that has been brought to its attention, perhaps by a user’s complaint. It may then conduct a follow-up inspection to determine whether the problem has been remedied.
At the end of an inspection, the FDA may issue a Form 483 if the investigators have observed conditions that they feel 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.
An 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 escalating enforcement actions. 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.
To avoid administrative and judicial actions, it is essential that your organization is fully prepared for FDA inspections.
One of the best ways to prepare for an FDA inspection is to conduct the type of training that builds a culture of compliance within your organization. This is the key element to ensuring that your employees, facilities, and processes all key elements of a robust Quality System are prepared to withstand a high level of scrutiny.
The optimal situation is when your employees are automatically acting in ways that are compliant with your quality system and with FDA regulations. It helps to think of training in the context of an athlete. Countless times, they perform the actions that enable them to compete at a professional level. It is this training that builds muscle memory, which is what you want to do with your staff. You want to build a mental memory of always doing things the right way to get the right result.
An important contributor to this training is conducting regular internal audits.
An internal audit is a self-check that is not a one-time event. To get the best results, it’s important that you have a continual auditing process in place. Your organization should be conducting Quality Systems internal audits quarterly or even monthly. There should be a group within your quality or compliance team that is responsible for performing internal audits to make sure that operation is staying on track with regards to compliance. Employees tend to veer off course from time to time, but the value of continual internal audits is to get those processes and employees back on course.
A significant benefit to conducting continual internal audits is that you reduce the chance that the FDA will identify observations resulting in a Form 483. To make sure that your organization has done all it can, it is helpful to also conduct third-party audits.
Third-party audits take your internal audits a step further. They help you take a proactive approach to protect your organization by finding and remediating issues before the FDA discovers them. If, on the other hand, the Agency has already found issues, then a subsequent independent audit can help your organization correct these issues and become compliant.
The value of third-party audits is based on their objectivity. Internal auditors who are associated with the development program may overlook or downplay the existence of significant issues. With their independent objectivity, third-party audits often provide a more accurate view of what is occurring within the organization. Third-party audits can also be conducted to mimic the scrutiny that the FDA applies.
Just like with internal audits, conducting third-party audits limits the FDA’s opportunity to find observations that can lead to a Form 483 and further enforcement actions that can adversely impact the organization.
It is essential that your organization takes corrective action on the observations made during internal audits and the recommendations you receive from a third-party audit. Ignoring observations and recommendations will certainly create an environment that fosters noncompliance and creates issues that the FDA, other regulatory agencies or your clients/customers will surely discover.
ProPharma is here to help you make sure that your organization has a robust Quality System and has remediated any issues potentially affecting the commercialization of your drug product before the FDA inspection occurs. When it comes to an FDA inspection, ProPharma wants you to always put your best foot forward.
You will get the most out of a third-party audit when you view it as a learning tool rather than an adversarial action. You are bringing in a partner who is showing your organization where it can improve. With the proper perspective, along with taking corrective and preventative action, your organization will naturally reduce the amount and severity of issues the FDA may discover during an inspection.
Contact ProPharma today to get an expert third-party audit and make sure you pass your FDA inspection.
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