Simulating Reality in Mock Inspections

Across the pharma industry, regulatory inspections happen all the time, and-with stunning frequency-sponsors find themselves on the short end of an inspection, which costs time and money. Can a failed inspection be avoided? Are there steps that can be taken to produce a successful outcome that allows an application to proceed? The answer to both of these questions is yes, and the way to achieve this is by conducting mock audits.

While many sponsors undertake mock inspections, most can improve the process and use it to yield valuable data and improve odds of moving the submission forward. Some foundational ideas should be considered to maximize the utility of a mock audit.

Understanding mock audit fundamentals

Mock audits should be conducted as early in development as possible; the end of the process is not the time for the first mock audit. From the beginning of the clinical process, a sponsor should conduct mock audits of its clinical suppliers. In addition, mock audits should also be done on an annual basis during the manufacturing process.

The mock auditor should behave like an FDA investigator. Asking the mock auditor to show up unannounced is a way to realistically gauge how the staff executes their responsibilities while interacting with a regulatory agency inspector.

FDA reviews a myriad of processes/systems during an inspection; identifying areas that require revision in advance of an actual inspection is time well spent. This exercise also provides staff an opportunity to clarify requests for information, identify areas that need to be addressed, or discuss observed gaps in information or processes being evaluated.

FDA does not cut corners and, therefore, neither should a sponsor. In order to get the most out of the mock audit, it is essential that the audit is conducted as thoroughly as possible and should follow the same process as an FDA audit.

Principles for success

The following five principles are necessary to the success of a mock audit.

All audits should be done by an independent auditor(s). Independent audits are important because they shine fresh light on the questions, “Are we doing the right things to stay in compliance?  Are we following our own standard operating procedures (SOPs)?” Audits help sponsors take a proactive approach to protect their drug development program by discovering issues and fixing them before they are found by FDA. If the agency has already found those issues, then a subsequent independent audit can help the sponsor stay on track toward compliance.

Mock audits should be used as a tool. Audits are diagnostic; they point out strengths and flaws in both processes and results. Most audits add to the strengths and fix the flaws.

The objectivity of the audit matters, which is why simply conducting internal audits is not enough. Audit investigators who are associated with the development program may overlook or downplay the existence of significant issues because it is in their best interest to do so. Overlooking trouble spots is far less likely to happen with an independent auditor.

Look at the system, not just the process. Good laboratory practices (GLPs), good clinical practices (GCPs), and GMPs are standards that envelop procedures put in place to ensure that products are tested and manufactured properly. However, simply having the appropriate SOPs in place is not good enough. These procedures must be followed to the letter, or the sponsor may have to deal with the consequences of one or more of its quality systems being noncompliant.

The essence of FDA’s regulations regarding quality is the need to have a quality assurance unit of some type. Obviously, different types and sizes of firms will have different quality functions. The key is to make sure that internal processes are controlled. That’s what an audit does: it verifies that control exists. Frequently, adherence to SOPs is the key to this. If those are regularly violated, it is likely that non-compliant outcomes will result.

Make sure the report is not buried. What good is an audit, if no one reads the report? Audits are treasure troves of information. They detail what works and what doesn’t. They describe what needs to be fixed and what problems may arise. And most of all, they serve as a road map to a better organization.

Sponsors should immediately act and remediate any areas identified in the report as having any deficiencies.

If the audit is in advance of an expected approval, move quickly. Unfixed errors fester. When one problem appears, others may follow. So, when a mock audit provides information about potential areas of concern, the problems need to be fixed as rapidly as possible. And if they can’t be fixed, then management must know quickly. The severity of the concerns will dictate how quickly the sponsor should proceed.

Despite their obvious importance, mock audits are frequently ignored in an attempt to cut costs; this makes no sense. The investment in time and money to assess practices is a necessary step. Mock audits guard the data and provide assurance to the approval process. The sponsor who skips these does so at their own peril.