The second in an ongoing series of regulatory updates by Larisa Pavlick, VP, Global Regulatory & Compliance, for the United Natural Products Alliance
Let’s start this expedition with a typical day involving the Food and Drug Administration (FDA). It is Monday morning at 10 a.m., and your receptionist has just notified you that a representative from FDA is here. Will you be ready?
What happens during an FDA inspection? How can you be prepared?
About FDA Investigators and Training
While all investigators are required to have a Bachelor’s degree and a minimum of 20-30 credits in science, previous experience is not required. I started, as all new investigators, with one year of studies including book work, computer based training, and on-the-job (OJT) training. During the first year, studies are primarily independent and self-paced. The list of mandatory training is called the “Bingo Card.” I have attached a redacted version of my Bingo Card for your review.
At some point during their first year, an investigator also attends “new hire” training. New hire training is a three-week course, which includes studies on the Food, Drug, and Cosmetic Act; Evidence Development; and Personal Safety. Near the end of the first year, an investigator is audited by a supervisor while conducting an inspection. This process is called a “Level One Audit.” After passing the Level One Audit, an FDA employee is then considered qualified to conduct independent FDA investigations and inspections.
After completing the Level One Audit, an investigator may be selected to attend specialized training on a specific commodity. An FDA-regulated commodity can include:
Dietary supplement training consists of a four-day course. When I took drug training in 2009-2010, it was a six-class series. Each of the six courses were two to three weeks long and training included site visits to some of the major pharmaceutical manufacturers to see the equipment and processes in person. Canned food training is about a week long; however, it requires several prerequisite classes including food-processing technology at Purdue University. Dietary supplement training is one of the shortest courses offered at FDA.
After attending any of these training courses, the investigator is qualified to conduct the inspection or investigation within each of these specialized types of facilities. If time and staffing permits, OJT training is conducted with a senior investigator to allow exposure to a new product or process for the new investigator with some oversight. A senior investigator is anyone who has been with FDA for longer than one year and has already taken the course. They do not necessarily have experience or background in the commodity. Dependent on district demands, OJT is not always available.
to conduct an inspection and investigation. Some of these references are updated on an annual basis. An investigator is expected to know, understand and follow the references while out in the field (i.e., onsite during a facility audit). They are designed for training the investigator; however, if the industry had access to the same materials, I felt they could be prepared and better understand the expectation during an FDA audit. How and (more importantly) why does the industry not know about these references?
These are public documents, and I have included links to each of them at the end.
Once I started conducting independent dietary supplement work, I verified with my supervisors that I could share these references with the facilities I visited. At first, it felt like I was sharing an insider secret. I began providing a copy of these references with nearly every firm I visited. I also tried my best to help them understand how to use them.
At the end of this document, I have attached a full list of my key references to help you to prepare for your inspection and plan to provide more information on each of these in 2017. In the meantime, I would recommend that you and your quality, regulatory, and operations staff bookmark these links, read each document and use them regularly.
Investigations Operations Manual
Your first key reference is the Investigations Operations Manual, Chapter 5 - Establishment Inspections. This manual is commonly called the IOM by FDA staff. The IOM is a manual used by FDA to train employees for conducting an FDA inspection, and it is referenced very frequently during employment with the agency. Chapter 5 is 117 pages long. It outlines how the investigator prepares for their visit to your company and the type of information covered during the inspection. Subchapter 5.4 – Food describes all of the details regarding a food inspection and the areas covered, including personnel, plant and grounds, raw materials, equipment, manufacturing process, quality control, sanitation, employee practices and more. In Subchapter 5.10 – Reporting, you will see the type of information required in an Establishment Inspection Report (EIR). Reading this section provides key information regarding what questions you will likely be asked during the inspection. I hope that if you understand what the investigator is looking for, you will be able to prepare yourself and your facility.
Form FDA 482
FDA does not announce inspections or investigations. Agents will show up, present credentials (a metal badge and a two-part identification card), and suddenly your entire schedule has just been hijacked. The investigator will introduce himself or herself to your receptionist or whoever greets them. They must ask to speak to the most responsible person on-site. The most responsible person is the top of the corporate organizational chart. Typically, this is the president, owner or CEO. Although that person often does not stay actively involved during an inspection, the visit always starts with them.
What if the most-responsible person is not there? Will FDA leave or reschedule? No, the inspection will continue regardless of the presence or absence of the most responsible person. The investigator will issue the Form FDA 482, Notice of Inspection, to the most responsible person, regardless of what level of management or authority they have. Typically, once senior or executive management arrives, the investigator will be introduced; however, they do not need to be present to begin the audit process.
Once the most responsible person is identified, the first step for the investigator is to issue the Form FDA 482. This form is a three-page, carbon copy form with small legal print related to the Food, Drug, and Cosmetic Act. I have attached a link to an example below. The small print explains essentially why FDA has authority to conduct inspections at your facility. The form is completed by the investigator with your company’s legal name, address and the most responsible person's name and title, plus the date and time the inspection began. The investigator will sign and print their name and title on the form and provide you with the original. They will retain the copy. After the FDA 482 is issued, the inspection has officially begun.
Next: Common questions about an FDA facilities’ inspection.
References and other helpful links
Compliance Program: Dietary Supplements-Importport and Domestic (Implementation Date: 03/26/2010) includes Pen & Ink Changes as of 07/08/10 to Parts I and II
An example FDA Form 482 – Notice of Inspection
Investigations Operations Manual Chapter 5: Establishment Inspections
Key Inspectional References
21 Code of Federal Regulations Part 111
PART 111—CURRENT GOOD MANUFACTURING PRACTICE (GMP) IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS
21 CFR Part 110: Food GMPs
Biennial Food Facility Registration Renewal (October 1-December 31, 2014)
Food links including labeling
A Food Labeling Guide, Guidance for Industry
The FSMA Technical Assistance Network (TAN) is now operational and providing technical assistance to industry, regulators, academia, consumers and others regarding FSMA implementation. The website is found at http://www.fda.gov/Food/GuidanceRegulation/FSMA/ucm459719.htm