Following an FDA inspection, you may be issued an FDA Form 483, a form listing Inspectional Observations of current issues and/or potentially problematic conditions.
First and foremost, it’s important to take these observations seriously. Although it does not represent the FDA’s final determination on compliance, deciding not to respond to FDA 483 observations within the 15-business day window will almost certainly result in a Warning Letter or further enforcement action.
While crafting a strong response is crucial, keep in mind it’s just one part of a larger recovery process. Grab our free white paper: The Emergency Guide to FDA Warning Letters & FDA 483 for a comprehensive guide to FDA 483 recovery.
Before we jump into what makes a response effective and compelling, let’s briefly go over proper layout:
3 Parts of an FDA 483 Response
The structure of your response should follow this 3-part outline:
In this introduction, respectfully thank the FDA for identifying opportunities for continuous improvement and clearly state your obligation to comply with the law through commitment to action. This should be written by senior management.
Restate each observation and include the following for each one:
- Background information regarding the observation
- An assessment of the root cause of the problem or commitment for further investigation if additional time is needed, with target dates for completion
- Corrective actions, immediately corrected if possible with completion dates and objective evidence to be included with attachments or attainable target dates for completion
- Preventive actions (particularly for any systemic issues found)
- Reference to objective evidence to be included as attachments for each completed action
- Commitment to provide a follow-up response, per specific date, if all actions cannot be completed prior to the 15-day submission timeline for the initial response
List of Attachments
Clearly describe and identify any attachments you provide. The numbers and names referenced in the body should exactly match the number and name in the list.
Attachments should be easy to find, read and understand. For example, if an SOP is attached, reference the specific section(s) that address the issue in the body to make it easy for the reviewer. Avoid forcing them to search through reams of documentation to understand your improvements.
Working with this basic outline, here are 5 essential things to keep in mind when crafting your response:
1. Be clear.
While the details of your response depend on the particular observations cited, it should specifically respond to each observation, be easy to follow and leave no doubt about what you intend to do to resolve the situation.
2. Be compelling.
Typically, the most effective way to write your response is in narrative form.
State the observation and address it in a clear, chronological format allowing you to put your company in the best light possible.
3. Anticipate potential questions.
Your response should first focus on addressing the central issues raised in the observations and provide accurate, objective evidence that anticipates and answers the potential questions your action plan lays out.
3. Carefully manage disputes.
If you decide to dispute an observation, you must be prepared to back it up with enough factual, objective evidence to be convincing.
Never ignore an investigator’s claims. Even if you believe something may be inaccurate, your response should clearly provide enough explanation required to show exactly why you do not concur with the observation.
4. Support all claims with facts and hard data.
Every claim and response you make in your response must be backed up with objective evidence.
Unsupported or poorly explained assertions are of no value to the FDA and only raise more doubts about your ability to resolve the problems identified.
5. Assess your response for quality and thoroughness.
Proofread, edit and re-work your response before submission to ensure it is as complete and compelling as possible. Even one typo or inaccurate statement can reduce the FDA’s confidence in your ability to provide high quality products to the market and protect the public, increasing the likelihood that a Warning Letter will be issued and potential escalation to enforcement action.
To ensure perfection and objectivity you may choose to seek the help of third party experts to conduct an independent assessment of the thoroughness and acceptability of the response prior to submission.
Want to learn more about responding to FDA 483 observations and crafting an effective Corrective and Preventative Action (CAPA) Plan? Grab our free whitepaper: The Emergency Guide to FDA Warning Letters & FDA 483 or contact our team to consult with an expert.