Writing 483 Response can be a stressful process. However, it is beneficial to follow a systemic process to ensure that the response is adequate.
The first step is to conduct a marketed product assessment to determine if 483 observations have any adverse impact on the marketed product. If there is an impact on marketed products, then a field alert report (FAR) or Biologic Product Deviation Report (BPDR) needs to be filed in 3 days and 45 days, respectively. A response to FDA-483 is to be submitted in 15 business days, therefore calculate quickly when the response is due to the agency.
The second step is to determine if there is a need for an interim response before 15 days. For significant issues that impact multiple marketed product lots, data integrity, and/or other systemic issues, an interim response demonstrates a commitment from the company. The interim response can be provided with a final response. The key is to communicate the company’s position and meet its commitments. For serious observations, a meeting with a district/center regulator is beneficial.
The third step is defining a strategy for responding to the observations. It is good to take time to read the 483 and understand the issue instead of start writing a response. First, read about all issues and understand if there is a systemic concern. Involve relevant individuals, departments, and teams in writing the response so that all the information is reviewed.
Once you have understood the systemic issues, start writing a response. Confirm and double-check if the proposed action addresses not only mentioned issue but also systemic issues also. Take a holistic view and deep dive into the issue (zoom in and zoom out) to determine if there is a quality system failure.
Initiate a CAPA to conduct root cause analysis, remediating, correcting, and preventing the issue. Determine if interim controls are needed while CAPA is being implemented. Include an effectiveness check in the CAPA plan to ensure that implemented CAPA is effective and there is no reoccurrence of issues. Agencies expect global CAPA, so it is important to ensure that these corrections are applied to all sites and locations, globally, if applicable.
For CMO/CTL or other critical outsources operations, include in your quality agreements the ability for you to review the response before submission to FDA. Review the final response for correctness. If multiple writers are involved, then harmonize the styles.