A primer for dietary supplement manufacturers, own brand distributors and ingredient suppliers.

While the truism “You never get a second chance to make a first impression” has been attributed to both Will Rogers and Oscar Wilde, it is rarely disputed that that an initial encounter sets the tone for all future interactions and that it is difficult to change someone’s first perception once it has been formed. This holds just as true for U.S. Food and Drug Administration (FDA) investigators coming into a facility to do an inspection as it does for anyone else.

Background

According to the agency’s mission statement, FDA has an exceptionally broad public health mandate that calls upon the agency to “ensure the safety, efficacy and security of human and veterinary drugs, biological products and medical devices; and by ensuring the safety of our nation’s food supply (including dietary supplements and dietary ingredients), cosmetics and products that emit radiation.” FDA is also responsible for regulating the manufacturing, marketing and distribution of tobacco products to protect the public health and to reduce tobacco use by minors.

These responsibilities and attendant authority are conveyed upon FDA by the Federal Food, Drug and Cosmetic Act (FDCA), and can be traced back to the Food and Drug Act of 1906. Today, when an investigator arrives at your facility to conduct an inspection, he/she is there under the FDCA’s grant of authority to enter, at reasonable times, any factory, warehouse or establishment in which food, drugs, devices, tobacco products or cosmetics are manufactured, processed, packed or held, for introduction into interstate commerce or after such introduction, or to enter any vehicle being used to transport or hold such food, drugs, devices, tobacco products or cosmetics in interstate commerce for purposes of enforcing the law and any related regulations. In essence, if your facility is operating, FDA has the authority to conduct an inspection. And FDA utilizes this authority: During fiscal year 2023 FDA conducted more than 500 inspections related to compliance with Dietary Supplement Good Manufacturing Practices, 21 CFR Part 111. The number of inspections related to food is even higher when 21 CFR Part 117, Current Good Manufacturing Practice, Hazard Analysis and Risk-Based Preventive Controls for Human Food (HARPC), which applies to dietary ingredient producers, is considered. As should be obvious from this information, when FDA comes to your facility, it is just one of many that are being inspected as part of the agency carrying out its obligations under the FDCA and you are not being “picked on.”

Starting the Inspection

Upon arrival at your facility FDA will approach reception just like any other person entering the facility, at which time they will identify themselves to reception. They will display their FDA identification and shields (badges) and advise that they are there to conduct a facility inspection and present the company with a notice of inspection (FDA Form 482). At this point, if you have properly prepared for this inevitable moment, your inspection plan/standard operating procedure (SOP) for inspections should kick in and your company should be in position to immediately demonstrate to the investigators that you are not afraid to have them in your facility because your company is comfortable with how its operations are run. A well thought out inspection plan will ensure that everyone who might interact with the investigators (including your reception desk) will know what to expect from FDA, understand their roles and responsibilities during the inspection, and understand their own and the company’s rights. (For example, company financial information and employee records other than training documentation are confidential and cannot be examined by the investigators).

Reception should know to contact the individuals who will have direct responsibility for interacting with the investigators: usually the company director of compliance and director of quality (who may be the same person). Senior management on site should also be alerted. The company representative who is authorized to accept the FDA notice of inspection, usually one of these individuals, should be notified. Many companies also have a system in place for alerting all employees in the facility that FDA is there. This is the equivalent of a “code blue” call in a hospital. Once these tasks have been accomplished, the investigators should be escorted to a conference room (assuming one is available) or another appropriate private area where the opening meeting can be held.

The Opening Meeting

Unlike the meeting that FDA will request at the end of the inspection (the closeout meeting) the opening meeting is something that is held at the company’s request and is an opportunity for it to place its best foot forward. The meeting should be held in an appropriately large area with a table that can be used for taking notes and spreading out papers. Ideally it will be equipped with a projector that can be used to show a PowerPoint presentation about your company. If a projector is not available, you should have copies of the slides printed and provided to all participants in the meeting. These should include the company heads of compliance and quality as well as any other department heads available at the time of the investigators’ arrival. If the facility being inspected supplies dietary ingredients or is otherwise subject to HARPC regulations, your preventive controls qualified individual (PCQI) should also attend the meeting.1 Introductions should be made to each of the individuals who will be accompanying the Investigators during the inspection.

The PowerPoint (or slide handouts thereof) should be the centerpiece of the opening meeting. It is your opportunity to brag about what your organization has accomplished. Many companies turn to top level management to handle this presentation. Whoever is chosen should be sufficiently senior to be a credible spokesperson and be comfortable speaking to an audience. Subjects that can be covered can include highlights of the company history (photographs of how a facility has grown can help make this presentation interesting). Significant upgrades in equipment and other operational improvements should be depicted. Introduction of senior management and managers with compliance responsibilities heads of quality and compliance, the PCQI, and any other individual(s) you feel are appropriate to highlight. Photographs and short biographical summaries of relevant experience, training and education can be helpful. The theme of this presentation should be to show that you are proud of your operations and project a clear, positive image of your company.

In addition to what might be covered in the PowerPoint, the following documents should be ready to give to the Investigators:

Organization Charts: Identify company ownership, “C-suite” officers, department heads and all employees with significant FDA Compliance related responsibilities. One thing that you will want to ensure is clearly depicted here is the ability for your quality/compliance heads to have direct access to senior management without having to go through production or sales.

Facility Floorplans: Ideally will show a well-organized, linear product flow with areas for quarantined material clearly identified and separated from released product. The investigators will almost certainly react positively to being provided with this information as it will allow them to plan to conduct the inspection most efficiently (a positive for the company as having the investigators leave the facility as soon as possible is highly desirable)

SOP Index: During the course of the inspection, it is inevitable that the Investigators will ask to review specific procedures used in your operations. These typically include cleaning procedures, procedures for the handling of allergens and the creation of batch production and master manufacturing records. Providing the index to the investigator is an opportunity to show that the company has a robust/fulsome quality program as reflected by a well-organized set of standard operating procedures (SOPs). The SOP Index is something that Investigators typically request during the early stages of an inspection and presenting it to them during the opening meeting allows the company to send another signal that it knows what it is doing and is confident in the high level of its quality program.

Food Safety Plan (Ingredient suppliers and others producing “food”): 21 CFR Part 117.126 provides that covered companies “must . . . prepare and implement a written food safety plan.” This work “must” be completed by one or more PCQI. Major elements of the plan include: A hazard analysis of the company’s operation; preventive controls, a recall plan and a supply chain quality and qualification program (including a specific foreign supplier verification program). As with the SOP Index, providing this document at the opening meeting is a signal that the company has top notch quality program and understands its compliance obligations.

Company Catalogs: Provide a way for the Investigators to get a quick overview of the company’s business and may limit the amount of time spent “wandering” around the facility looking to understand what is being produced.

Once the opening meeting is concluded, the inspection will begin in earnest. The investigators will go off into the facility (always accompanied by company representatives) with what should be a positive impression and a feeling that the company understands its regulatory obligations and has a solid culture of compliance.

Conclusion

If you are prepared and have a plan in place, there is no reason to be anxious when FDA arrives at your facility. You can be confident that you will be in position to create a favorable impression of your business and set a positive tone that should last through the entire inspection, making the process as painless as possible. NIE

Reference:

1 The PCQI is responsible for developing and implementing the facility’s food safety plan as mandated by HARPC regulations.

Attorney Marc S. Ullman represents clients in matters relating to all aspects of U.S. Food and Drug Administration and Drug Enforcement Administration matters, regulatory issues, Federal Trade Commission proceedings and litigation. He practiced with one of New York’s leading white collar criminal defense firms for 10 years, where he represented clients in both federal and state prosecutions, as well as numerous related civil matters and other litigations. He can be reached at [email protected].