Today, The Porch takes you behind the scenes of a typical FDA inspection. Many that are new to FDA inspections (and, most global regulatory inspections would be similar) and even some that have been around the block are not aware of some of the interactions that occur during these inspections. I have been personally involved in over 100 of these inspections myself, most of which I was the lead company representative. Plus, I have a number of friends and acquaintances that are or were FDA investigators, so I think I can paint a pretty accurate picture of what really goes on during these inspections.
Following are ten sets of questions/answers around typical FDA investigators and the inspections they conduct. Keep in mind that these answers are for TYPICAL situations, not all.
- What preparation occurs by the FDA investigator prior to the presentation of the FDA-482 form for an inspection at your facility? Most FDA investigators do spend time preparing ahead of the inspection. In some cases, this preparation is extensive and may require a week or more. Investigators will examine the firm’s file and review the most recent inspection and any company responses or correspondence. They will note the verbal recommendations made during the last inspection. They will also review any Field Alert Reports, recalls, or other issues communicated to the District Office. Additionally, many investigators will review results of inspections for other manufacturing sites in other locations or Districts for your company. For example, if a Warning Letter was issued at one of your sister sites, the investigator will likely review the issues noted and the company response to determine if follow-up at your site is needed. Don’t assume that the investigator merely walks into your facility “cold.” They will likely be very aware of your compliance position and have a list of potential concerns or issues that they will examine during their time on-site.
- What is the motivation or driving factor for the typical FDA investigator? Are they looking to make a name for themselves to advance their own career or is it something else? I think most individuals in industry assume that FDA investigators advance their careers based on the number of FDA-483 citations they provide. This is not the case. Most good investigators are motivated by their desire to ensure the safety of the consuming public. They are concerned with any cGMP violations, but especially those that could harm a consumer. Their primary focus is whether our products are acceptable as measured by their safety, purity, effectiveness, labeled strength, and labeled identity. In short, they are most concerned with product quality. They may cite more minor cGMP violations on a FDA-483 form, but their primary interest is to ensure that we perform in an overall manner that will prevent a negative impact to our consuming public. Sure, there are some investigators that are looking for ways to enhance their own standing within the agency, but more investigators are intent on serving the public by ensuring we do what we should and what we said in our regulatory filings.
- Is it really possible to influence the outcome of the FDA investigation by how the investigation team manages the investigation? The answer to this question is a clear and definitive “Yes!” I have seen many inspections turn positive or negative simply by how they were managed. When the investigator develops a trust in the management team, feels that the team is open and honest, and believes that the information provided is accurate, the inspection will almost always be more collaborative, positive, and productive. When the investigator feels the company’s inspection team is deceptive (trying to hide something), manipulative (screening out negative information), or hindering the inspection (by preventing access to information or facilities), the inspection almost always turns negative. In fact, when the investigator believes any of these is the case, they can now take even more aggressive action that is supported by more recent regulations. So, be open, be honest, work diligently to share everything requested, and seek to demonstrate integrity in managing the inspection. I know of one situation in which the firm was told directly by the District Office Compliance Officer that a Warning Letter would not be issued merely because the District believed in the integrity of the Quality leadership at the site. Yes, integrity does matter!
- What does the FDA investigator do with all the documentation they collect? Most of the mountains of documentation collected during an inspection is destroyed after the inspection is closed by the District Office. So, what purpose does it serve? There are really three purposes for the documentation collected during an inspection:
- To allow further study of potential compliance concerns during the time between on-site visits during a multi-day inspection
- To document compliance (or non-compliance) activities noted during the inspection (e.g., proof of concerns noted in any potential FDA-483 observations)
- To facilitate the final report after the inspection (Establishment Inspection Report or EIR)
- What does the FDA investigator do between leaving your facility for the day and arrival the next at your door? Most investigators spend some time reviewing their observations for the day before arriving the next day. If they are traveling to your site, it is not uncommon for investigators to spend much of their evenings reviewing documentation, making notes about potential concerns, and preparing for their reviews the next day. In many cases, the investigator is communicating with their supervisor or Compliance Office about findings and the direction of the inspection for coming days. It is the rare investigator that does no preparation before arriving the next day.
- Would you rather have a highly experienced and knowledgeable investigator inspect your facility or one that is less experienced and less knowledgeable? Why? Personally, I would rather have an experienced and knowledgeable investigator inspect my site. These investigators can more accurately and quickly focus on potential issues, their experience allows them to better understand what we do and why, and they tend to need less background information to grasp the concepts of more complex operations and activities. And, these investigators are less prone to citing less significant issues. However, because of their experience, they are more likely to quickly identify more significant issues that could evade a less experienced investigator. So, depending upon your situation, there are advantages to either. Nonetheless, we have no choice in who inspects our facilities, so this is something we have little ability to influence.
- How have FDA inspections and investigators changed over the last 40 years? Many years ago, FDA investigators all covered many different regulated industries, such as pharmaceuticals, medical devices, food, blood, medicated feeds, etc. They had to learn the regulations and have adequate knowledge of all of these to properly function. Today, they tend to be experts in one industry. For example, now, investigators tend to focus on pharmaceuticals or medical devices or foods. Thus, they have the opportunity to learn about varying packaging techniques, dosage forms, manufacturing techniques, etc. in a way that allows greater depth of expertise. Additionally, FDA tends to recruit more individuals with advanced degrees or industry experience. FDA training programs also provide more in-depth knowledge than 40 years ago. So, on the whole, FDA investigators today tend to have more knowledge about their specific areas of expertise than the investigators of the past that had to have more breadth. As a result, investigations today are more focused and directed. For example, investigations often focus on specific systems. So, an investigator that has just inspected other firms have a solid basis of comparison to assess whether we are fulfilling “current” expectations.
- What causes an FDA investigator to lose sleep at night and why? FDA investigators take their responsibilities very seriously! The thing that concerns them most is failing to detect GXP violations that ultimately result in safety or health concerns. They never want to be personally responsible for missing a potentially serious issue during an inspection. Thus, you can see why most are so diligent in focusing on issues that most clearly could harm consumers (e.g., data integrity, sterility, foreign contamination, labeling, dosing, etc.).
- Why do we see so many different approaches taken by FDA investigators (e.g., some want to be collaborative; some are aggressive; some use inspection guides; some merely follow the flow; etc.)? Though FDA inspection guidelines are pretty specific in what investigators should consider examining during an inspection, they do not remove the ability of investigators to use their individual talents to conduct investigations. As a result, some focus on procedures, some on data, some on checklists, some on manufacturing, etc. And, the individual personality of the investigator will often determine the flow and collaboration of the inspection. Typically, the investigator is patient and collaborative as long as you provide information openly and efficiently. I have witnessed a few investigators that are not so patient and collaborative, no matter how the inspection is managed. In these cases, you must remain professional, calm, and continue working efficiently. You must not allow that rare rude or impulsive investigator to intimidate you into mistakes or misstatements.
- What is the goal of the typical FDA investigator? For them, what constitutes a successful inspection? Most investigators are just like us… they have a job to do and simply want to get it done thoroughly and completely. They are not normally trying to do more than that. We must realize, though, the gravity of their job which is to protect the ultimate consumer of our products. We should attempt, as much as possible, to help them accomplish that task, yet without exposing more information than is requested. Realizing their goal can help us manage the inspection and how we interact with the investigator.
Hopefully, this post has helped you understand better the typical FDA inspection and the inspection approach. When we better understand what is really occurring, we can better manage the flow and content of the inspection.
Have a great day!
(If there are questions that you have about FDA or global regulatory inspections not covered here, please feel free to contact me at firstname.lastname@example.org. I will try to help you get your answer directly or through a future edition of The Porch.)