Pharmaceutical Manufacturing 101: Surviving an FDA Inspection
By Paul Eichholz
In follow up to our recent blog post, entitled “Pharmaceutical Manufacturing 101: How to Prepare for & Manage an FDA Inspection,” part two of our blog series will discuss additional ways to prepare for an inspection, as well as address some critical post inspection activities.
Conducting Mock Inspections
It is essential that a war room or coordination room is used to manage the inspection process during a mock inspection. The war room coordinator must be someone that is familiar with all aspects of the site, is organized, and is good at documenting requests for information, data, procedures, documents, and other items that may be requested by the investigator.
It is important to test the war room with a significant number of requests in order to prepare the team for the stress and volume of requests received during an inspection. In addition, it is critical to ensure that the documents going into the inspection room are correct, contain only the information requested, identify potential themes or the direction the inspector is taking the inspection, and prepare for the next day. The war room coordinator must maintain an accurate log of all of the items that are requested and ensure copies are made and filed in the inspection binder so it is clear what items were requested. It is not uncommon for the same document to be requested more than once during an FDA inspection, especially if more than one FDA investigator is involved. Handling a mock inspection in the exact same manner an FDA inspection will be handled is a must.
Daily Inspection Close-Out and Next Day Preparation
Even when the investigator leaves for the day, the inspection process is not complete. Once the investigator(s) have indicated that they are getting ready to wrap things up for the day, the firm’s management should request a daily close-out of the inspection. Items to focus on or request additional information on include:
- Any potential concerns the investigator has to date
- Items the investigator desires to review or discuss upon their return to the facility
- Verification that everything that was requested to date has been provided
If the investigator mentions any potential concerns, the firm should work to address and correct the issue before the investigator(s) return.
Documents supporting any actions taken while the investigator is gone should be reviewed and staged so they can be provided immediately upon the investigator’s return. Asking about items for discussion allows the firm to stage and review documents that might be requested, prepare SMEs for any discussion or questions, and provide the investigator with information quickly as it is requested.
Verifying that there are no outstanding requests allows the firm’s inspection team to confirm what was provided and file and store documents that are no longer needed. The firm should also determine if the documents remaining in the inspection room are still needed and remove any unnecessary paperwork immediately.
Hopefully no substantial issues are identified, and the investigator does not issue an FDA Form 483 upon the inspection’s completion. During the closeout it is important to listen to everything the investigator says regarding any observations and begin working to address them immediately.
If the firm believes any of the information contains any errors, it is acceptable to ask for clarification of the observations; but it is not recommended that firms attempt to argue about the validity of the observations during the closeout. Rather, firms are advised to wait until the Form 483 is received, at which point they can compile a response that fully addresses each observation identified. Any applicable documentation or evidence regarding how the issues were addressed should be included in the response. It is important that the response clearly indicates what attachments apply to what observation. This can be done by linking the two items in an index. Although a response to an FDA Form 483 is not required, failing to respond is not a wise decision. As such, firms should submit a response via certified mail within 15 business days of receipt of the Form 483.
Should the FDA accept the response, the firm should receive the Establishment Inspection Report (EIR) upon closure. Receiving the EIR is official confirmation that the FDA has accepted the firm’s response, and agrees that the firm took the appropriate actions. The EIR is a valuable tool that is often overlooked when preparing for an FDA Inspection. It provides significant details regarding:
- What the inspectors looked at.
- Concerns or questions they might have had that did not result in an observation.
- Discussions about any refusals a firm might have received regarding providing information requested by the inspectors.
The EIR should be filed with the response and reviewed as part of the inspection readiness program for the next inspection.
If the inspection yields a significant number of observations, or the observations are critical in nature, it is best to seek assistance from an outside firm specializing in quality and compliance issues. Seeking support from a third party also indicates to the FDA that you take the issues seriously and are committed to addressing them in a timely fashion. Should your organization find yourselves in this position now or in the future, contact us right away, we can help. Learn more about The Weinberg Group’s GMP auditing services.