The Food and Drug Administration is the federal agency charged with ensuring the safety of food, medication and other consumable products. In carrying out its duties, the FDA conducts both inspections of plants and facilities. These inspections may be conducted as a matter of course or, in some situations, are initiated in response to a reported problem.
Regardless of the reason for the FDA’s visit, a failed inspection wreaks havoc on the business strategy of both fledgling and well-established businesses.
Given the importance of an FDA inspection, manufacturers should develop a comprehensive set of standard operating procedures to be employed during an FDA inspection audit. Having a plan in place will ensure that all key managers and employees understand the FDA inspection process and its importance.
It will also help them understand what types of issues the FDA inspectors are looking for and how to guide them in their investigation without allowing them to roam freely throughout the manufacturing facility, which could lead to the discovery of unrelated problems.
The FDA Investigation Process
The FDA investigation process begins with the issuance of Form 482. FDA Form 482 essentially provides notice of an FDA audit to the manufacturing facility. The form is completed by the FDA inspector who will be conducting the audit. The form will cite statutory authority that gives the FDA the ability to audit the facility.
It will also contain a brief description of the inspector’s expectations. Once completed, the form will be provided to top-level management or the highest-ranking person at the facility at the time.
Once the FDA auditor begins their inspection of the facility, they will note their observations on FDA Form 483. While Form 483 contains the inspector’s findings related to any potential violations of the Food, Drug & Cosmetic Act, it is not the inspector’s final report.
If the inspector took any samples during the investigation, they must complete FDA Form 484 and provide it to the same individual who received form 482.
Types of FDA Inspection Audit
As noted above, there are several different types of FDA inspection audits. A company’s response to an FDA audit should depend, in part, on the nature of the inspection. There are four types of FDA audits:
Pre-Approval Inspections: A pre-approval inspection is initiated when a company submits a request to market a new product. During a pre-approval inspection, the FDA auditor visits the facility to ensure that all the information contained in the company’s filings is accurate. The FDA inspector will also determine whether the facility is suited to manufacture the new product.
Routine Inspections: The FDA conducts routine inspections based on the predetermined level of risk a facility presents.
Compliance, or Follow-Up Inspections: A compliance inspection is essentially the FDA’s attempt to determine whether facility management appropriately responded to a previous investigation. For example, if an inspector visits a facility and issues an FDA Form 483 noting several deficiencies, the FDDA will conduct a follow-up inspection to ensure the management addressed the concerns noted in the form.
For-Cause Inspections: As the name implies, a for-cause inspection is the FDA’s response to an adverse event or report indicating that there may be a compliance issue at the facility. For example, if a company issued a recall after a product was alleged to have caused serious injury or death, the FDA may conduct a for-cause inspection. For-cause inspections can also result from an employee’s report that the facility is not in compliance with the Food, Drug & Cosmetic Act.
Advance Preparations for an FDA Audit
In some ways, FDA inspections are no different than other federal government investigations in that, by the time a company realizes an investigation is underway, there is little that can be done to prepare. Thus, it is best for management to plan for an FDA audit and implement a set of standard operating procedures that will position the facility for a positive inspection.
As a preliminary matter, the FDA wants to see that a facility is prepared for an inspection. If an FDA auditor sees that management is prepared and appears unfazed by their presence, it indicates that management has nothing to worry about. On the other hand, a facility management team that is scrambling on the spot to provide the inspector with what they are asking for, or otherwise appear to be unprepared, will give off the impression that compliance is an afterthought.
Along those lines, it is imperative that all facilities subject to an FDA audit develop a concrete plan for both routine, follow-up, and surprise visits.
Standard Operating Procedures of an FDA Inspector
From the moment an inspector arrives at a facility, management should ensure that they appear ready for the inspection. Below are a few things management teams can do to prepare for an FDA audit.
Assemble an Inspection Response Team
The first step to FDA inspection readiness is to create an inspection response team. For example, management should identify who the inspector should speak with when they arrive at the facility and how the rest of the management team will be notified of the inspection.
Additionally, an inspection-response team should include quality-control personnel as well employees or managers from all aspects other the facility to ensure a cohesive plan throughout the organization. One member of the investigation response team should be assigned to accompany the inspector throughout the facility, and a separate person should be assigned as a scribe. The scribe will document everything that the inspector asks to review and make note of all topics raised during the audit.
Designate Workspace for the Investigator and the Response Team
One of the most common mistakes management teams make when preparing for an FDA audit involves a failure to provide the inspector with a designated suitable workspace. Nothing indicates a lack of preparation more than scrambling to find an empty office or conference room for the auditor.
Also, facility management teams should set aside a separate workspace for the inspection response team, which is not immediately adjacent to the inspector’s workspace. This is because, regardless of advance preparation, the unartful convening of an investigation response team may give off the impression a facility was unprepared for the inspector’s visit.
Identify the Documents the Inspector Is Likely to Need
One of the most important jobs of the inspection response team is to consider what an FDA inspector will want to review. Developing a list of material in advance allows the investigation response team to compile the information in a user-friendly way that will indicate the facility was prepared. To the extent possible, arrange all documents in chronological order and rely on visual aids such as graphs and charts.
If an inspector asks to review certain documents or data, the person assigned to interact with the investigator should hand off the task of gathering the data to another member of the team. This way, one member of the team will remain with the auditor while the other members of the investigation response team assemble the requested information outside the investigator’s presence.
Come Up with Explanations in Advance
An FDA investigation response team should think in advance about the hot topics that the inspector may want to cover during their visit and develop compelling explanations for all decisions surrounding these issues. High-level management may be able to skillfully articulate the basis for a decision; however, it is important that the person meeting with the inspector can also do so. Thus, this is an area that may justify role-playing to ensure that an employee or mid-level manager is not caught off guard by a particularly difficult question posed by the inspector.
Resolve Any Noted Deficiencies in a Timely Manner
It is common for an FDA investigator to make several findings in an FDA Form 483 after an inspection. While the severity of these findings varies based on the circumstances, it is crucial that a company immediately begin to address any deficiencies.
In fact, according to the FDA, “corrective actions or procedural changes that were accomplished immediately in the presence of the investigator are regarded as positive indications of your concern and desire to voluntarily correct discrepancies.” Thus, it is never too soon to begin implementing changes to address an inspector’s concerns. While this may not be possible in every instance, an FDA investigation response team should come up with ways to cut through any corporate red tape and make changes on the spot.
Retain Counsel for Assistance with Preparatory Efforts
The inspection process is exceedingly complex. The above steps are crucial; however, it goes without saying that a facility’s management team needs to command an in-depth understanding of the business as well as the regulatory environment to effectively navigate an FDA investigation. Often, facility management possesses the required knowledge of the business; however, the FDA rules and regulations pertaining to the business may be beyond the scope of their familiarity. This is where the assistance of an experienced FDA investigation and compliance attorney is key.
An attorney can help management teams better understand the FDA inspection audit process on a macro level. What particular issues will the inspector want to discuss? How have similarly situated companies fared during the investigation process? And how did these companies address any deficiencies to the satisfaction of the FDA?
FDA audit attorney Dr. Nick Oberheiden explains, “Preparation is key when it comes to FDA audits and investigations. While a company’s management team is in the best position to explain the business, they may not know how to address all the potential concerns of an inspector. In fact, they may not be aware of common deficiencies found in other facilities operating within the same industry. When selecting an attorney to assist in the FDA inspection preparation process, it is important that a firm select a law firm that not only has a track record of successfully assisting companies through an FDA audit but also has specific experience working with companies in their specific industry.”
For companies subject to FDA inspection audits, few investigations present higher stakes. For this reason, a firm should do everything possible to prepare. Not only that, but the first impression the company gives off is crucial. Small organization details that may not necessarily be relevant to an FDA inspector’s underlying compliance concerns can go a long way in making it through an FDA audit.
