FDA Form 483 Observations & Warning Letters
Whether you’re vaccine or drug manufacturers, facilities that conduct clinical trials, or a medical device company manufacturing Class II or Class III devices, you can expect random and routine inspections by the FDA.
Preparing for an FDA inspection is a critical step, and ProPharma Group experts can guide you through the entire process. It’s what happens after the inspection that we are addressing here.
One unfortunate thing that can happen after an FDA inspection is receiving 483 Observations, and the potential of receiving a Warning Letter. It is important to understand the differences between the two and what you can expect as a result.
What are FDA Form 483 Observations?
An FDA Form 483 Observation, also referred to as “inspectional observation” or “Form 483” is sent by the FDA to highlight any potential regulatory violations found during a routine inspection. An FDS Form 483 Observation can relate to the company’s facility, equipment, processes, controls, products, employee practices, or records.
While an FDA Form 483 is not final determination on regulation violations, they are cause for concern and need to be addressed with urgency. The financial impact of an FDA Form 483 Observation can be catastrophic, sometimes costing companies several million dollars. If the issues are systemic, the FDA Form 483 Observation can trigger training, redesign, process implementation, and other measures.
It is better to anticipate any potential issues that might result in a 483 Observation by creating and implementing processes to avoid this scenario. Trying to repair the issues brought forward as the result of a 483 Observation is not only expensive, but very disruptive to the company, often negatively impacting employee morale.
Several months after the inspection, the company may receive the Establishment Inspection Report (EIR). Before leaving the facility, the inspector will submit any FDA Form 483 Observations. Upon receipt of the FDA Form 483 Observations, the company has 15 days to respond.
What to Do After Receiving an FDA Form 483 Observation
If you receive an FDA Form 483 Observation, the situation needs to be handled with care. First and foremost, you should review the documents with the inspector before he/she leaves the facility. You do not have much time to address these challenges, so having a full understanding of the documents and what needs to be done to correct the issues is critical.
Before the inspector leaves, be sure to:
- Gain an understanding of observations noted and assure their accuracy
- Understand the broader message the FDA is sending
- Identify and discuss any errors in the observations
- Ask questions
- Demonstrate awareness of applicable regulations
- Consult with legal counsel as necessary
FDA Form 483 Observations need to have a comprehensive written response to FDA with completion dates. It is also good practice to address your response to the district director with a courtesy copy to the lead investigator. When responding, you may present challenges or questions about the observations. If sufficient information is provided, observations may be removed from the FDA Form 483.
Send your response within 15 days, or the FDA will not be required to consider your response in their decisions for subsequent actions. Once your response is submitted, the FDA will review the Form 483 Observations along with an Establishment Inspection Report and your response. The agency will use this information to determine what further actions to take.
What is an FDA Warning Letter?
An FDA Warning Letter is an official deficiency letter from the agency, which is sent by the investigators of the agency. Companies may receive this document in the mail, without prior notification from FDA. Before a Warning Letter is issued, the FDA requests the company to comment on the deficiencies listed in the Form 483 Observations found during the inspection. If the FDA judges this response to be unacceptable, a Warning Letter will be issued.
Typically, FDA Warning Letters are sent to ensure overnight delivery and receipt of delivery (e.g., return receipt requested, FedEx). As with an FDA 483 Observation, the company has 15 days maximum to respond in writing. However, if the cause of the Warning Letter is severe, the FDA may shorten the deadline.
FDA Form 483 Observations and Warning Letters are sometimes mistakenly identified as the same thing. Like FDA Form 483 Observations, Warning Letters can be very costly and can significantly delay time to market and consume capital in the process. However, FDA Warning Letters are more serious than Form 483 Observations because they represent an escalation of the process. As such, agency feedback from an FDA Warning Letter should be addressed immediately.
What to Do After Receiving an FDA Warning Letter
Once the FDA has determined that a company has significant violations to their regulatory policies and issued a Warning Letter, in order to remedy the issues raised, the following steps should be taken:
- Determine the root cause of the items listed in the letter
- Develop an action plan to remedy issues if one has not been developed. If a plan has been developed, modify it accordingly
- Have a high-level person in the quality group prepare a written response to the Warning Letter
- Have other people not involved with the inspection review the letter
- Ensure that personnel in high-level management are carbon copied when the letter is sent
The response to the FDA Warning Letter should contain an opening statement that discusses how the company is serious about resolving the issue, what the date of the inspection was, and what the address of the site was.
The letter should also include a context for the situation, a restatement of the observation and the reference number, and a discussion of any related operations that were compliant.
Other content in the response letter depends on whether corrective actions have been taken yet and how long the corrections would take. For instance, if the corrections would take several months, the letter should include what measures personnel are going to take to be compliant in the interim.
Have You Received an FDA Form 483 Observation or Warning Letter?
Whether it’s an FDA Form 483 Observation or a Warning Letter, addressing the issue will require a lot of work, and can be very stressful. You may want to consider engaging the assistance of outside experts like ProPharma Group to help your team through the process.
Our experts can help you monitor your sites, provide independent auditing to prepare for an FDA inspection, and train your team to ensure everyone has a strong understanding of the regulations.
We have extensive experience and can serve as an extension of your team, supporting you throughout the entire product lifecycle, or offering assistance with one particular area.
If you have received an FDA Form 483 Observation or Warning Letter, or you just want to take proactive steps to avoid one, contact us today to discuss how we can help.