If one of your clinical research sites has received an FDA warning letter or FDA Form 483, your first instinct may be to panic. It may also be tempting to look for someone to blame, which is equally unhelpful.
First, take a deep breath. While an FDA Form 483 is less formal than an FDA warning letter, both serve the same purpose to inform you of issues that require corrective action. What matters most is how you respond to those concerns.
How To Respond To An FDA Warning Letter Or Form 483
1. Respond On Time
A response is not required for an FDA Form 483, but providing the FDA with a formal response is good practice. If received past 15 days of issue, the agency will not consider the response in their decision on subsequent action. A due date will be noted in a Warning Letter, usually 15 calendar days. An extension can be requested with justification of why more time is needed.
2. Focus On The Importance Of The Warning
Take the 483 or Warning Letter seriously and understand the larger message the agency is sending. A Form 483 includes inspectional observations listed in descending order of importance. A warning letter indicates a more serious violation that requires prompt corrective action.
Both point to broader issues that may include failure to follow the investigational plan, failure to maintain adequate records or another potentially serious problem.
3. Assign A Response Team
The letter or Form 483 will most likely be addressed to top level management or the principal investigator. Those ultimately responsible should assign a group to review and draft a response to the FDA’s findings. They should be actively involved in the development of the response and any correction action plans developed.
4. Consult With Legal Counsel If Necessary
This is especially important if findings affect product and public safety. As the history of clinical research demonstrates, researchers have a responsibility to protect human subjects above all else.
5. Respond In Descending Order of Importance
Take the agency’s example and respond to the most serious issues first. Then address each issue as it is listed in the FDA Form 483 or Warning Letter.
6. Take Responsibility
Accept responsibility as top level management or principal investigator. Not passing the buck will demonstrate recognition of seriousness of violations and your commitment to comply with applicable laws and regulations.
7. Address Each Item Individually
Don't attempt to group individual issues together, even if they seem related. Cite each item separately in your response.
8. Identify Correct Causes Of Findings
Thoroughly investigate the root cause of the findings noted. Don’t just pick training because it seems to be the easiest, most identifiable culprit. Take the time to look into the processes and systems of your organization and correctly identify the cause.
9. Develop Corrective Action Plans
Describe corrective action plans to address each citation listed. Describe the steps to address other areas that may be subject to the same deficiency. Include how each action plan will be measured for efficacy.
10. Set Obtainable Goals
Develop corrective action plans that are reasonable for your organization with timelines that are realistic. Assign management to individual correction action plans or develop teams of employees to implement plans and assess the effectiveness. Again, the agency may follow-up and will issue additional Warning Letters for incomplete or ineffective action plans resulting in additional violations.
How A Contract Research Organization Can Help
Once you have responded to a Form 483 or FDA Warning Letter and outlined your plan for corrective and preventive action, you may want to consider enlisting a third party for help.
A contract research organization (CRO) like IMARC 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.
Our team has specific expertise in a wide variety of medical device trials. We can serve as an extension of your team, supporting you throughout the entire clinical trial life cycle or offering assistance with one particular area.
If you have recently received a Form 483 or Warning Letter or you just want to take proactive steps to avoid one, contact us today to discuss how we can help.
Do you have additional tips or tools for responding to FDA Warning Letters or Form 483s? Have any of these tips worked for you when responding to the FDA?