February 24, 2016
February 24, 2016
Imagine for a moment that this is your current situation…
You receive a frantic call from the receptionist at your facility, an Investigator from the Food and Drug Administration (FDA) has just arrived for an inspection of the site.
Now take a moment to think about the circumstances…
Are you prepared? Is the investigator's arrival going to cause panic, turning into a chaotic experience for your firm?
Whether it is for the approval of a new drug or a routine inspection, an FDA inspection should not be a painful experience. Ensuring that any regulatory inspection is a positive experience starts by creating a culture of compliance throughout the firm, and continues with on-going preparation and frequent inspection readiness practice.
When it comes to being prepared for an FDA inspection, the rubric "practice makes perfect" does not apply on its own. It's a combination of practice and preparation that makes the difference. An organization that is routinely successful in FDA inspections incorporates all aspects of compliance into its company culture, and has leadership that supports this culture on a daily basis.
As a pharmaceutical company, living a life of cultural compliance provides the foundation for a successful FDA inspection. The likelihood that a firm will be successful during an FDA inspection diminishes greatly in companies where compliance is not a priority. Although it is possible that an organization could get through one or two inspections, it is not likely that the success will continue if its day to day culture doesn't demand compliance.
Does your firm have Standard Operating Procedures (SOPs) governing how to handle regulatory inspections? The answer should be: "Yes, there are procedures governing regulatory inspections, and all site personnel receives some type of training on these procedures." Individuals who are most likely to interact with an FDA inspector should receive more detailed training on the regulatory inspection process. It is also important that everyone on site understands what happens when an investigator arrives for an inspection, including who should be contacted and how to interact with the inspector.
The initial interaction with site personnel sets the tone for the rest of the inspection. Personnel who are confident in what they are expected to do, react calmly to the inspector's arrival, and follow the site's procedure for handling an inspection are noticed by an investigator. This illustrates that the site takes the inspection seriously and that they know how to handle an inspection. Demonstrating control and preparedness indicates that compliance is an ongoing management priority.
Your firm should have a Site Inspection Management Team (SIMT) to handle all regulatory inspections. If you are a virtual firm, does your Contract Manufacturing Organization (CMO) have a dedicated SIMT? If the answer is no, you should be concerned about the CMO's ability to successfully handle an inspection.
The SIMT should be comprised of individuals from several different areas and departments. The roles and responsibilities for each individual should be documented and the individuals should be trained and tested regarding their responsibilities. In addition, having a well-developed internal audit program is also a useful inspection readiness tool.
Members of the SIMT should include, but are not limited to:
One of the most critical members of the SIMT are the Subject Matter Experts (SMEs). SMEs must be identified and selected based on their ability to completely and clearly answer questions from an investigator. It is important that they are not selected based on the length of time they have been at the facility, whether or not they are the department head, or due to the fact that they have the most knowledge about a particular subject or system.
SMEs must answer concisely, providing only the information that was asked for in a confident and intelligent manner. SMEs should also be well versed in answering questions about specific systems, issues, or challenges at the site, should they be asked by the investigator. Being able to appropriately address challenges and risks at the facility is critical to a successful inspection.
The SME must also perform well in stressful situations. How will they handle a question they do not know the answer to? Will they make up an answer that they think the investigator wants to hear? It is important for the SME to realize that if they cannot answer a question that is asked by the investigator, they must respond appropriately. In this type of situation, the SME should simply state that they are unsure of the answer, but will either get the appropriate answer and provide it or find the individual who is able to answer the question.
Furthermore, investigator questions should be answered using the facility's SOPs. A typical response would be, "I am confident in the answer, but I want to verify that in the SOPs." This shows that the SME understands how to use the SOPs, as well as their contents and purpose.
Regardless of the criteria used to select SMEs, a firm does not want to select the person that tends to say too much, volunteer information that wasn't asked for, complain constantly, and/or does not act in a confident and professional manner when interacting with an investigator. SMEs should be trained regularly using simulated or mock inspections to ensure that they are ready for an actual inspection at a minute's notice.
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.
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:
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:
The EIR should be filed with the response and reviewed as part of the inspection readiness program for the next inspection.
Successful regulatory inspections do not just happen, they require a company culture built on sustaining compliance, significant training and preparation, and flawless execution during the inspection. Most firms have challenges or issues of some type. It is how they are handled and addressed during an inspection that can be the difference between a successful inspection and enforcement activity taken by the FDA or other regulatory agencies.
If your 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.
TAGS: Regulatory Sciences
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