The Food and Drug Administration (FDA) is the federal agency charged with ensuring the safety of foods, medications and other consumer products sold in the United States. In carrying out its duties, the FDA conducts both surveillance inspections and audits of plants and other facilities. While the FDA conducts many of its inspections and audits as a matter of course, it also scrutinizes companies’ facilities and manufacturing processes in response to reported problems.
Regardless of the reason for the FDA’s visit, a failed inspection or audit can not only disrupt a company’s business operations (if the company is forced to stop selling an adulterated or otherwise noncompliant product), but it can also lead to administrative, civil, or criminal enforcement action.
“Preparation is key when it comes to avoiding unnecessary consequences during FDA inspections and audits. While a company’s executives and managers may be in the best position to explain the business, they may not know how to address all the potential concerns that can arise during an FDA inquiry. An experienced FDA compliance attorney will be able to serve in this role while also helping ensure that the company is prepared to defend itself effectively.” – Dr. Nick Oberheiden, Founding Attorney of Oberheiden P.C.
Given the risks that FDA inspections and audits present, manufacturers and other companies should develop a comprehensive set of standard operating procedures to be deployed when the FDA launches an inquiry. Having a plan in place will ensure that all personnel have a clear understanding of their role in the process, as well as clear instructions for what to do (and what not to do) to help ensure that the FDA’s inquiry does not lead to adverse outcomes that could—and should—have been avoided.
The FDA Inspection Process
The FDA inspection process begins with the issuance of FDA Form 482. This form provides notice of an impending site inspection that will take place at a particular plant or other facility. The form is completed by the FDA inspector who will be conducting the inspection; and, along with identifying the facility, manufacturing process, and data integrity to be inspected, it will cite the FDA’s statutory authority to examine the facility’s grounds, operations, and records for purposes of assessing federal compliance. FDA Form 482 will also typically 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.
After issuing FDA Form 482, the FDA inspector conducting audits will begin their inspection of the facility, noting 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. Additionally, if the inspector takes any samples during an inspection, they must complete FDA Form 484 and provide it to the same individual who received the initial FDA Form 482.
Once the inspection is complete, the inspector will issue a final report noting any alleged compliance failures. The form and substance of this report will vary depending on the purpose and nature of the inspection, as well as the inspector’s findings. If the inspection results in any findings of noncompliance, the company that owns the facility will usually be given a grace period to come into compliance (unless any noted violations present substantial public health or safety concerns), after which the FDA may take deny registration, initiate an enforcement action, or take other appropriate responsive measures based on the circumstances involved.
Types of FDA Inspections and Audits
There are four main types of FDA inspections and audits. A company’s response to an FDA inspection or audit notice will depend, in part, on the nature of the inquiry. The four main types of FDA inspections and 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 inspector visits the various aspects of 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, such as medical devices, for clinical trials.
- Routine Inspections: The FDA conducts routine inspections based on the predetermined level of risk a facility presents. The scope of these inspections (and the potential risks involved) depend on the level of risk a facility presents as well.
- Compliance (or Follow-Up) Inspections: A compliance (or follow-up) inspection is essentially the FDA’s attempt to determine whether a company has adequately remedied findings of noncompliance from a prior inspection or audit. For example, if an inspector visits a facility and issues an FDA Form 483 noting several deficiencies, the FDA will conduct a follow-up inspection to ensure that the company has fully 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 FDA issues at a particular facility. For example, if a company issues a recall after a product is alleged to have caused serious injury or death, the FDA may conduct a for-cause inspection at the facility where the product is manufactured. For-cause inspections can also result from an employee’s report that the facility is not in compliance with the Food, Drug & Cosmetic Act.
Preparing for an FDA Inspection or Audit
FDA inspections are similar to other federal government inquiries in that, by the time a company learns an inspection is underway, there is little that can be done at this stage to prepare. As a result, proactive preparation is essential. To ensure that they will be prepared to respond to (and “pass”) an FDA inspection or audit when necessary, companies should adopt a set of standard operating procedures that they can execute once they find out that an inspection or audit has been scheduled.
As a preliminary matter, the FDA wants to see that a facility is prepared for an inspection prior to the product approval. If an FDA auditor sees that a company is prepared and has sufficient documentation on hand to affirmatively demonstrate compliance, this will typically set the stage for a smooth process and favorable outcome. Conversely, if a company’s personnel are forced to scramble to provide the inspector with what they need to evaluate compliance, or if it is clear that they don’t have adequate documentation available, this will raise additional questions and concerns. Of course, certain aspects of compliance (or noncompliance) will be evident from the company’s facilities as well—and this underscores the importance of a comprehensive and detail-oriented approach to the preparation process.
The following are all key steps for avoiding unnecessary adverse outcomes during an FDA inspection or audit:
Assemble an FDA Inspection Response Team
The first step to FDA inspection readiness is to assemble an inspection response team. 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.
An inspection response team should also include quality control (QC) personnel as well as employees from all areas of the facility to ensure a comprehensive and coordinated approach to compliance and a cohesive plan for responding to the FDA’s inquiry 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 to take notes. The latter should document everything that the inspector asks to review and make note of all topics raised during the inspection or audit.
Designate a Workspace for the Investigator and the Response Team
One of the most common mistakes companies make when preparing for an FDA audit involves failing to provide the inspector with a designated suitable workspace. Companies should also set aside a separate workspace for the inspection response team that 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 documents the FDA’s inspector will want to review. Developing a list of documents in advance will allow the investigation response team to compile the documents in a user-friendly way that will demonstrate both compliance and preparation. 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.
The company’s legal counsel should be involved in this part of the process as well. While it is important to provide FDA inspectors with the documentation they need to accurately assess compliance, it is equally important not to share information unnecessarily. Not only can this potentially result in the scope of the inspection or audit being expanded, but it can potentially jeopardize the attorney-client privilege and other protections as well.
Prepare Responses to the FDA Inspector’s Anticipated Questions and Concerns
The FDA investigation response team should work with the company’s outside counsel in advance to identify the issues that the inspector will likely want to address during their visit. As necessary, the response team should also work with the company’s counsel to prepare to address any issues that are likely to give rise to compliance-related concerns. While senior executives may be able to skillfully articulate the basis for a decision, 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 or audit. While the seriousness of these findings can vary, it is crucial that the company immediately begin to address any and all deficiencies, regardless of their potential implications.
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 undertaking immediate corrective measures may not be possible in every instance, the FDA investigation response team should work with the company’s outside counsel here, too, to try to find a way to implement an appropriate corrective measure as efficiently as possible.
Retain Experienced FDA Regulations Compliance Counsel is Essential
The FDA inspection process is both complex and high-risk. As a result, experienced legal representation is essential.
An attorney who has significant experience representing companies during FDA inspections and audits will be able to help the company’s senior executives and investigation response team members better understand the FDA inspection process and ensure that they are thoroughly prepared. What particular issues will the inspector likely want to discuss? How have similarly situated companies fared during the investigation process? How did these companies address any deficiencies to the satisfaction of the FDA? How quickly should the company be able to implement appropriate corrective measures? These are all key questions that require insights gained from past experience.
While insights gained from past experience can be invaluable, it is also critical to keep in mind that every situation is unique. Not only do different circumstances present different risks, but the FDA is also constantly refining its inspection and audit processes to address new public health concerns and enforcement priorities. Thus, even if a company has been through an FDA inspection or audit previously, this doesn’t necessarily mean that its next experience will be similar. Experienced legal counsel will be able to assist here as well—from identifying issues that have the potential to create problems to assisting with resolving these issues as proactively as possible.
