Using Mock Inspections to Prepare for FDA GCP Inspections

Food and Drug Administration good clinical practice inspections can happen to anyone involved in conducting clinical trials in the United States. Even the most meticulous organizations experience a feeling of apprehension when faced with the prospect of having their operations, employees, and data scrutinized by federal investigators. These fears are not unfounded. If serious deficiencies are discovered, the consequences could jeopardize a study or a submission.

An FDA inspection will never be easy, but the experience will be much less traumatic when the people involved are trained to meet the requirements and pressures of the inspection process. One of the most effective ways to prepare for this challenge is by using mock inspections. By creating a learning experience that accurately simulates an inspection, an organization can test its response procedures and bolster employee knowledge and confidence to handle a real inspection more effectively.

Why the FDA conducts inspections
The FDA inspection programs cover the gamut of organizations involved in the clinical trial process, including clinical investigators, sponsors and monitors, contract research organizations (CROs), laboratories, and institutional review boards. Guidelines and FDA compliance program manuals (see FDA Compliance table) detail the various types of FDA inspections. Although the rules and regulations seem complex, it helps to remember that all inspections are designed to answer a few key questions.

• Is the organization knowledgeable of, and adhering to, the federal laws and regulations governing clinical trials?

• Are the safety, rights, and welfare of trial subjects being protected?

• Can the validity of the clinical data supporting a New Drug Application (NDA) or Biologic License Application (BLA) be confirmed?

• Was the targeted study well controlled and conducted according to applicable protocols, standard operating procedures (SOPs), and regulations and guidelines?

• Is complete documentation available to support all of the organization’s training, monitoring, and compliance programs?

When FDA investigators inspect a facility, they expect the organization to be able to supply timely and complete answers in support of these basic questions. Accomplishing that task quickly and efficiently, however, requires planning and practice. The time to begin preparing for FDA inspections is not the day your organization receives a Form FDA-482, Notice of Inspection. By designing and implementing a training program for FDA inspections in advance, you will better prepare your organization to meet the demands of any inspection.

Preparing for an FDA GCP inspection
Your FDA inspections training program should include several components. A good place to start is an employee training course on FDA inspections. Whether designed and taught by internal personnel or an outside instructor, the course should provide information your employees need to understand the basics of the inspection process. Topics might include:

• the regulations governing inspections and the agency’s authority.

• the different types of inspections, the reasons behind FDA inspections, and what the agency is looking for.

• the “anatomy” of a typical inspection.

• the types of information and documentation that might be required.

• the people who would be involved in working with the investigators.

• a review of “dos and don’ts” for the inspection.

• common FDA inspection findings.

• the possible consequences of negative findings (including negative consequences for the organization).

Supporting information can be found in the FDA’s compliance program manuals (see table). The manuals spell out guidelines for inspections of various organizations and are the framework for all bioresearch-monitoring inspections.

Another important part of your preparation should be the creation of an SOP for government inspections. The SOP should cover every aspect of your organization’s actions during an inspection, such as what happens when an investigator arrives, the roles and responsibilities of each person involved in an inspection, the process(es) for retrieving and reviewing requested documents and data, actions that are permitted and not permitted during an inspection, how the inspection is documented, and the response and follow-up procedures for a Form FDA 483, Inspectional Observations. A well-designed SOP for inspections will guide your employees’ actions during the inspection and help you provide a well-organized response.

The third component of your education and training efforts should be “mock FDA inspections”-that is, conducting a simulated inspection that reflects the real experience as closely as possible. While classroom-training programs are valuable, most people who have been through an FDA inspection say that nothing quite prepared them for the intensity of the real thing. The pressure of having every aspect of your study activities and documentation scrutinized can be stressful, even intimidating, for everyone involved. In addition, although FDA investigators do not necessarily try to make the inspection process difficult, their role in maintaining the integrity of U.S. pharmaceutical products means that they take their jobs seriously.

The benefits of mock GCP inspections
Mock inspections are a good way for your organization to provide a training experience that approximates the intensity of a real inspection. In essence, a mock FDA inspection is a role-play that casts an individual in the role of an FDA investigator who conducts an inspection “in character” and helps the organization live through a simulated FDA inspection. This type of experience is valuable for a number of reasons. It allows you to test your “inspections SOP” under realistic conditions and to determine whether it covers the process completely and provides the guidance people need to respond to the situation quickly and appropriately.

It also gives you the opportunity to analyze your logistic capabilities, corporate procedures, and information systems to determine whether they can handle the documentation and data demands of an inspection in a timely fashion. As a result, you can identify and correct weaknesses and can enhance your systems and procedures before their shortcomings inflict damage on your organization.

Another important benefit of mock inspections is their ability to make the inspection process more real to those who have never participated in one. With the experience of mock inspections, your employees will have a much better idea about the types of questions they might be asked, what role they should play, and how they should react in various situations. They will also have a greater appreciation of the seriousness of the inspection process and its importance to your organization. With that combination of knowledge and practice, there is a much greater likelihood that they will respond properly and handle their roles professionally during an actual inspection. Participation in mock inspections should also reduce the anxiety level of those who are later involved in real inspections. It should be noted that a successful inspection depends primarily on good quality data and having knowledgeable people available to present the data to the FDA.

Realistic role-playing is vital if you are to realize these and other benefits of your mock inspection program. This is especially true in the case of the person playing the role of the FDA investigator. By remaining “in character” throughout the mock inspection, the instructor sets an important example for the rest of those involved to act as if the inspection is real, which greatly enhances the education value of the exercise. The person you select to be the mock investigator should have experience with FDA inspections, as well as an in-depth understanding of the relevant FDA guidelines. If you are selecting from your internal resources, this would usually be someone in your quality assurance (QA) group. You should also look for an individual who will be enthusiastic about the role-playing aspect of this assignment.

Executive-level management support is another essential ingredient for the success of a mock inspection program. Because these exercises require a substantial investment of time and effort above and beyond your employees’ regular duties-and a certain amount of disruption at the inspection site-senior managers must make it clear that they strongly support the program and must encourage employees to invest the energy and dedication necessary for it to succeed. Executive support can be demonstrated through personal participation in the mock inspection and by allocating funds for the educational effort, as well as by giving the participants the flexibility to participate fully.

Conducting a mock inspection
Once your educational programs and SOPs are in place, you will need to select studies to subject to the mock inspection. The selection criteria used by the FDA are good guides. A typical choice would be a recently completed pivotal Phase 3 study that included a significant number of subjects. Also consider the accessibility of study data and the personnel who would be involved if a particular study were selected. The goal is to choose studies that fairly represent the type of work your organization does and that also will provide an accurate test of your people and infrastructure.

After you select a specific location and study, develop a plan for your mock inspection, based on your SOP and the appropriate FDA compliance program manual. The plan should clearly state the objectives of the inspection, the project and location selected, the people who will participate, and time frames for completing the inspection. Pay special attention to developing the requests for information that your mock inspector will issue, keeping in mind the key questions about regulatory knowledge, data validation, adherence to SOPs, and documentation of compliance. Most important, incorporate an educational program into the mock inspection process. Decide how and when the participants will be “debriefed,” and how you will follow up on the lessons learned from the exercise.

When you actually conduct the mock inspection, try to make it as real as possible. Follow your plan, and treat the mock FDA investigator exactly as you would treat the real investigator during an actual inspection-from the time he or she walks into the building until the inspection is completed. Everyone should try to stay in character throughout the process to maximize the learning experience.

Inviting managers, executives, and people from other projects to sit in on the mock inspection is also useful. They can observe the inspection as part of the educational process.

Wrapping up
Because the mock inspection is an educational exercise, an immediate and thorough review of the lessons learned is absolutely vital following the inspection. This review can occur at the end of each day of the mock inspection, or at its conclusion, but doing the review while the details are still fresh is essential. This review process should include:

• comments from the person playing the FDA investigator about what was done well and where improvement is needed.

• observations from the QA team and others who observed the proceedings.

• input from the participants, both on what happened during the inspection, and on the value of the exercise itself.

• the creation of an action plan about how to address the compliance concerns and organizational shortcomings revealed during the mock inspection.

• a follow-up report to ensure that the action plan is being implemented.

During the debriefing process, your team should address any negative feelings that may have resulted from the mock inspection. Even though it’s just a training exercise, a realistic mock inspection can sometimes upset people or leave them feeling that they were unfairly singled out or criticized. Some may also be concerned that any problems uncovered during the mock inspection will somehow be held against them. The executives and managers involved in the exercise should make a special effort to reassure the participants that the results will not create repercussions in their job. Without this assurance, the value of future mock inspections could be compromised by employee reticence.

Because such mock inspections should be an ongoing part of any clinical organization’s training program, management support and employee participation in the program is vital. By holding these exercises periodically, more people can share the learning experience, and the organization can continually improve its level of preparedness for real inspections, as well as improve its operational systems.