Speaker 1: Hello, my name is Bill Guthrie and I'm the Director of Business Development at Compliance Insight, a leading FDA regulatory and quality assurance consulting firm. Joining me today to discuss preparing for an inspection is Melissa Schneider, Associate Director of Compliance at Compliance Insight. Hello, Melissa.

Speaker 2: Hi, Phil. How are you?

Speaker 1: Good. Thanks for joining me. Melissa, to start with, maybe can you just share with us your background and maybe your employment history or anything you think would be relevant about your experience?

Speaker 2: Sure. I've been in FDA regulated industry for about 30 years and that covers, I really specialize, I guess, in pharmaceuticals. I have a little bit of medical device experience and biologics experience as well.

Speaker 1: The title for our discussion today is the FDA inspection before, during, and after. So maybe we can just start, you can share with us the types of inspections, maybe how many have you been involved in, what types? Sure.

Speaker 2: I've been involved in many different inspections. I know we're specifically talking about FDA inspections today, but I've also been involved in many different types of customer inspections as well as international types of regulatory inspections as well. And I think they're all relevant to this topic because I feel like preparing for an inspection is pretty similar, whether you're preparing for FDA or other type. Now, the number of inspections I've been involved in, it's probably in the hundreds.

Speaker 1: Excellent. And I guess as we begin to talk about the before part of the FDA inspection, maybe share with us, I'm sure one of the biggest questions people probably have is how often will the FDA come to inspect me if I'm a manufacturer?

Speaker 2: Right. Right. And I get asked that a lot. Their schedule is developed on a yearly basis. They really like to hit, if you're having a general GMP inspection, they like to hit manufacturers once every two years. Now, obviously they occasionally get delayed, but a general GMP inspection, you can expect about every two years.

Speaker 1: And how do they decide who they're going to inspect? Kind of in what order? Like, is there any sort of determination used as far as who and when?

Speaker 2: Right. Right. It's not just the flip of the quarter.

Speaker 1: Right. Exactly.

Speaker 2: Yeah. They determine inspection priorities. Like I mentioned, they put together their inspection kind of planning at the beginning of the year, just like we do in industry. And they base it on risk. So what might prioritize your risk as a manufacturer or as an FDA registered facility? Risk level could be based on previous inspections. If you had a lot of inspection findings or those inspection findings were high priority or critical inspection findings, if you've had a lot of customer complaints or complaints to the FDA from either industry or customers, things such as that, or if the product you make is a higher risk product. So let's say if you're in the pharmaceutical industry, maybe you make an opioid or some other more potent drug product. Or if you're in the medical device industry, maybe you make an implantable or something else a little more critical. Those types of things can elevate your risk as well.

Speaker 1: Awesome. Thank you. And again, keeping our discussion in the sort of prior to the inspection, you know, one of the ways to be successful, obviously, is planning, right, and planning is critical. We know there's two types of inspections, right, that the FDA does. There's sort of the general and the pre-approval, right, or more of a planned inspection. As far as more of the surprise inspection or general inspection, can you share with us what we can do to plan or prepare, I guess, because you can't really plan, but maybe preparation is a better word. What can we do to prepare?

Speaker 2: So I always like to be inspection ready. And there are numerous things that we can do, whether it's a like pre-approval or for-cause inspection or general GMP inspection. One of the things you can do is have a robust internal audit plan or program, making sure that you understand your own faults so that anything the FDA or other inspectors may find is not a surprise to you, that you've got corrective actions in place or a plan to fix any problems because everybody has issues, right? We all have improvements that we can make. So that would be number one. Number two would be having kind of a binder or place where we keep common documents or common things an inspector may look for. And what I'm talking about is like a table of contents for standard operating procedures, an org chart. These common things, we keep them up to date, a list of deviations. These kinds of things are items that any inspection is going or inspector is going to look at, maybe our quality manual. If we've done any kind of annual reporting to the FDA, those types of things, keeping them up to date, keeping them available, keeping them in a common place. So when the inspector asks for it, it can be immediately provided and you're not fumbling or having to create the report. Those types of items, it makes you look really organized and really prepared.

Speaker 1: So it sounds like all of the things that you mentioned as it relates to preparation for a surprise inspection would carry over obviously to the scheduled inspection, but is there anything additional perhaps that we can do? Like maybe do we move our gap assessment schedule up if we have a planned inspection, right? We have a date on the calendar, would we perhaps perform a mock ahead of that or just ahead of that or making sure we give ourselves remediation? Is there anything additional or is it because certainly you thoroughly covered being inspection ready all the time, right? And that concept.

Speaker 2: For a planned inspection, I like to reach out to the inspectors. Now sometimes they're willing to give you this information and sometimes they're not, but I always like to ask what they're going to inspect. Can they provide you with an agenda? That allows you to prepare. If it's an FDA pre-approval inspection, you know they're going to be specifically looking at a range of items. So this specific drug product. So you'll want to prepare everything and anything related to that specific drug product. If it's just a general maybe a supplier approval audit or something along those lines, again reaching out, getting an audit agenda, and then collecting as much documentation surrounding what you do for that client or for, you know, maybe if you do FDA things and other items that are not related to the FDA, focusing on that FDA documentation. We expect them to look at if we've had previous inspections, what kind of CAPAs did you put in place? What kind of corrections did you make? You know, gathering that information and putting it together. So there are definitely ways to prepare.

Speaker 1: Awesome. Thank you. So let's move into what we should do, I guess, during the inspection. So auditors here, they're at our front desk. It's a surprise inspection. What's the first thing we should do?

Speaker 2: So one of the key items is making sure everyone is prepared. So I always like to do and routinely update this training, make sure everyone in the plant knows how to interact with the FDA, just on a basic level, that anyone who may greet the FDA knows where we're going to put the FDA or other inspectors, that we don't want them just wandering the plant, that we may have a conference room in which we'll put them, that we're going to have who to contact, you know, whether we contact Quality Assurance or other head management people, you know, that there may be a group email that goes out to let everyone know that FDA is on site. What are the specific steps? And that really should be written up in some sort of formalized document. Because when the FDA walks in the door, the energy level shifts, right? There's almost a little bit of a panic or excitement or something along those lines. Sometimes people don't think straight. So you want to have some sort of work instruction or SOP that people can follow. And they know who to call or who to contact and exactly what process to follow. The credentials of the FDA should be checked. You want to make sure that they are who they say they are. We should also check they should have a Form 482 that states what type of inspection. Is this a preapproval inspection? Is this a general GMP inspection? Is this a for-cause inspection? That should be presented as well. And then if this is a multi-day inspection, we may want to do some sort of wrap-up every day if possible. What did we cover today? Were there any findings today? And what might they want to cover the next day? Perfect.

Speaker 1: Thanks, Melissa. So I know at one point I received some really great advice that when I'm being inspected to only answer the question being asked. But maybe we can just talk a little bit about specific things that you should tell the auditor. Maybe things to avoid or, you know, I don't know, maybe it's all about style. I don't know. But essentially just not giving out more information maybe than is being asked. I don't know if that's a good piece of advice, but certainly what advice would you give to people in talking to an inspector? Right.

Speaker 2: So you want to pick your company representatives very carefully. You want to make sure, and there are different types of people, right? In my experience, there are always the people who want to fill their time or fill blank spaces with conversation. Those are not the types of people that you want in an FDA inspection. In my experience, auditing or hosting an audit can be really boring. You know, you present the auditors with some documentation and they will sit and review it and the room may be very quiet. It may be tension filled. And you don't want a person who cannot deal with that quiet time, right? So anyone who feels the need to talk or converse or provide unsolicited information is not the person you want in the room. So along that same vein, you want someone who can answer the question, answer the question completely and concisely, but then stop with the information.

Speaker 1: And we're looking for a good courtroom witness, right?

Speaker 2: Exactly. Exactly. Yeah. Unfortunately, when the FDA audits, they're also collecting evidence. You know, it's funny that you bring it up that way, but that's exactly what they're doing. If they find something egregious at your plant, all of that documentation that they've collected does become evidence against you, unfortunately. So we want to give them exactly what they asked for, give them complete information, you know, certainly not falsified information, but not additional information. So let me give you an example. If you've got a log book, maybe a three ring binder that has all of your information from 2021 for all of your equipment, maybe it's something you're doing temperature monitoring on and the FDA asks for just the temperatures for March of 2021 for a specific piece of equipment, you would not bring that whole binder into the room and present it to the FDA. You would want to specifically pull out that one log, or maybe it's two or three pages of logging of those temperatures for that one specific piece of equipment that document March of 2021. If you present the whole notebook to the FDA, then they have the right to look at all of that information, even though they've only asked for one month of one piece of equipment for 2021. So you need to be very careful how you answer questions, but also how you present information.

Speaker 1: Thank you. So you talked about the multi-day inspection, and I think one of the things you talked about was the importance of basically having not a closeout, but certainly a summary of the day's activities towards the end of the day. Any other things that we should be aware of as it comes to dealing with multi-day inspections?

Speaker 2: Sure, sure. One of the things I always recommend is that we have someone who is kind of the host of the audit, but we also have someone who is a scribe or a note taker. It's very difficult, I find, to answer questions as well as taking complete and thorough notes. And these people can change roles during the day, but you want to make sure you have a complete note taker as well as someone who's answering questions. You may also have subject matter experts that you pull in to answer questions on, say, a specific process or a specific test method or those types of things. At the end of the day, especially if it's a multi-day inspection, I like to summarize how that day's audit went. So taking those notes from that day's audit and just kind of writing up a couple paragraphs. Why do we do this? Because when you get to remediation, looking back at who said what, who responded in what way, what documents were presented to the FDA, having those notes to look back on is really critical. Because especially if it's a week or more, trying to think back on what was said and who said what is really a difficult task.

Speaker 1: Awesome. Thanks for that. So as we think about the end of the inspection, other than maybe heading to our local watering hole for a drink when the inspection's over, what's going to happen at the close of the inspection? What should we do once the inspector leaves the building? Anything we can do sort of right there post-inspection?

Speaker 2: Sure, sure. So the way the inspector closes the inspection, they do a closeout meeting. And generally, companies like to invite most of their key players to that closeout meeting. So everybody can hear what the FDA has to say. The FDA doesn't really expect you to respond during that closeout meeting. They just want to cover if they found any out-of-compliance situations. They'll present you with a 483. And this is basically just a list of observations. And so they basically list, it's like an audit report. They list it in the document and present it to the highest, it might be the president or the CEO, whoever is the highest level person at the facility. So that's kind of how the inspection closes out. And then the industry expectation is that within about 15 days, business days, you respond to those 483 items with a corrective action plan. So sometimes companies miss the mark with this one. They either try to respond to everything while the FDA is still on site, instead of focusing on really answering the questions for the FDA. They think it makes them look more professional if they get everything done right then, instead of taking the time to really do a good job of remediating. Or they don't respond, which can also harm you as well. So the FDA really wants you to do a thoughtful response, come up with an action plan, and respond in writing to that 483. And they usually provide you with who to respond to and how to respond. It's usually via email.

Speaker 1: Excellent. Well, Melissa, thank you very much. Any final words before we wrap up here today?

Speaker 2: No, I would just say, again, as I started out, making sure you're constantly prepared in an audit-ready state is really the easiest. I know that's not always the way industry operates, but it's always easier to be audit prepared than to scramble when you realize somebody's walking in the door or even calls to announce that they're coming to audit.

Speaker 1: Awesome. Well, thank you, Melissa. Really appreciate you joining me today. Thank you to everyone for watching or listening, and we hope you'll join us again on future episodes. Also, you can find us at www.compliance-insight.com. Both Melissa and my contact information is available there. We would welcome any additional questions or comments. Appreciate it. Bye-bye. Thanks.