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Pharma Trends: The Return of the FDA Warning Letters [Simone Ammons] Simone (George) Ammons
Yan Kugel is joined by Vincent Cafiso, the Director of Quality and Regulatory Services at CREO Consultancy and a former FDA investigator. Vincent shares invaluable advice on things never to say to an FDA investigator based on his extensive experience and expertise in the field.
Table of Contents
Vincent brings a wealth of experience to the table, having worked as an FDA investigator for six years. His passion for science and his deep knowledge of the pharmaceutical and medical device industry have allowed him to conduct hundreds of complex inspections, both domestically and overseas. His insights into the dos and don’ts of interacting with FDA investigators are invaluable for industry professionals.
During an FDA inspection, it’s crucial to maintain a confident and professional demeanor when interacting with investigators. Vincent emphasizes the significance of avoiding phrases such as “I think” or “usually,” as they can undermine the credibility of your responses. Instead, it’s essential to convey a sense of certainty and consistency in your procedures and processes.
In situations where you’re unsure about a specific question, it’s important to handle it tactfully. Vincent advises acknowledging the question and expressing your intention to provide a thorough and accurate response. This approach demonstrates your commitment to compliance and professionalism, even in uncertain circumstances.
Another critical point highlighted by Vincent is the importance of refraining from making disparaging remarks about past investigators or audits. This can create an uncomfortable and unproductive atmosphere during an inspection. It’s essential to maintain a respectful and professional attitude towards all interactions with FDA investigators, regardless of past experiences.
While it’s acceptable to build rapport and engage in small talk with investigators, it’s crucial not to let your guard down to the point of divulging sensitive information or compromising your professional stance. Maintaining a balance between building rapport and upholding professionalism is key to successful interactions during FDA inspections.
Vincent sheds light on the issue of following procedures that are in place but are ambiguous and lack detail. This can lead to inconsistencies in practice, and investigators are trained to detect such discrepancies. It’s crucial for companies to ensure that their procedures are clear, detailed, and reflective of their actual processes to avoid compliance gaps and potential issues during inspections.
Navigating FDA inspections requires a strategic and professional approach, as highlighted by Vincent Cafiso’s insights. By maintaining confidence, handling uncertain situations with tact, and upholding a respectful demeanor, industry professionals can navigate FDA inspections with professionalism and compliance. Vincent’s expertise serves as a valuable guide for industry professionals seeking to enhance their interactions with FDA investigators.
Vincent’s practical advice and real-world experience provide a comprehensive understanding of the dos and don’ts when engaging with FDA investigators. His insights are a testament to the importance of professionalism, confidence, and strategic communication during regulatory inspections. As industry professionals strive to uphold compliance and quality standards, Vincent’s guidance serves as a valuable resource for navigating the complexities of FDA inspections.
Episode Chapters:
Please be advised that this is an AI generated transcript and may contain errors.
00:26 – 01:13
Yan Kugel: Welcome to our podcast where we delve into critical insights for GMP professionals in the pharmaceutical industry. Today we have a special guest Vincent Cafiso and the Director of Quality and Regulatory Services at CERO Consultancy and he is a former FDA investigator. Vincent will be sharing invaluable advice on things never to say to an FDA investigator based on his extensive experience and expertise in the field. So join us as we uncover essential strategies and best practices to navigate FDA inspections with professionalism, compliance, and proactive mindset. So Vincent, hi, welcome to the podcast.
01:15 – 01:17
Vincent Cafiso: Yeah, thank you. Hi, how are you, Yan?
01:17 – 01:34
Yan Kugel: I’m fine. Thank you very much. So before we dive into the fascinating world of FDA investigations, what is your background there? How long were you there as an FDA investigator and how was the experience?
01:36 – 02:18
Vincent Cafiso: It was great. I did it for about 6 years. I started essentially right out of college. I loved science and I loved biology and anatomy and physiology and all of that. And so when I learned of this opportunity to use my science knowledge and my anatomy knowledge, it was something that really seemed very exciting to me. So I had a very early and exciting opportunity to do this. I did hundreds and hundreds of complex inspections of medical device and some pharmaceutical, mostly medical device, and some in vitro diagnostics as well. Many of those inspections resulted in
02:18 – 02:59
Vincent Cafiso: 483s and warning letters, some injunctions and some seizures and things like that. So a very exciting opportunity to work not only in New Jersey, which is where I was based at the time, but also to do inspections overseas at manufacturers that were looking to distribute their products in the United States, which is what gives FDA the jurisdiction over those international firms. So yeah, it was a great it was great opportunity, great experience. And of course, as I mentioned, doing hundreds and hundreds of inspections, meeting many thousands of people, you definitely hear a couple of things that
02:59 – 03:35
Vincent Cafiso: you think, maybe they shouldn’t have said that. So yeah, this is a fun 1, this kind of a topic. And of course, this particular post did very well with a lot of engagement. And I’m actually planning for a part 2, and a part 2, which is going to be created by the commenters. There were so many great comments and so many great suggestions of, well, you know, because my list wasn’t for 20, right? So I had a lot of people saying like number 21 XYZ, number 22 XYZ. Right. So I’m actually looking at those and I’m
03:35 – 04:08
Vincent Cafiso: aggregating those as we speak to see if I could put up a part 2. So it’s definitely a topic that gets a lot of attention and people really like to weigh in. Because I think being in pharmaceutical or being in medical device, as long as you’re regulated by the Food and Drug Administration, you have probably gone through an inspection at least once in your career. And so you could certainly think about what you may have heard that was really a good thing to say, but I’m sure you also would remember the probably more likely the things
04:08 – 04:12
Vincent Cafiso: that you probably should not have said or that 1 of your colleagues probably should not have said.
04:12 – 04:57
Yan Kugel: Right, exactly. So to give some background also to what you have said, you are very active on LinkedIn, and especially recently, and you have some great insightful posts about your experience. Some of them are humorous, and 1 of the most successful posts that you did, as you mentioned, was a list of 20 things you shouldn’t say to an FD investigator or it was a hit. And so I highly recommend already at the beginning of the podcast for you to follow Vincent. We will have his information in the overview of this episode. So check his profile. Follow
04:57 – 05:36
Yan Kugel: him. And part of this podcast, what we wanted basically to do is go over with you over some of the things you wrote in the post and analyze them a bit. Right. And 1 of the things that you wrote there that seems very, you know, something that nobody would think, basically saying, I think. So basically, you said that you should never say things like, I think that when interacting with an investigator. So what is it all about? And what is the reason for that?
05:37 – 06:16
Vincent Cafiso: Yeah, no, Yan, this is 1 that I put first because I think, and as I’m saying it now, right, I think That is something that people generally like to say because they don’t like to maybe seem too forceful or they don’t like to seem too definitive. But during an inspection, there are certain questions that you’ll be asked And those questions are generally going to be either open-ended questions where an investigator and by the way, all investigators are highly trained in how to do investigative interviewing. So they’re asking you specific questions that they know will be a
06:16 – 06:51
Vincent Cafiso: yes or no answer, but then they will also ask you questions that they know are going to be a little bit more open-ended where they will ask you a question like, tell me about whether or not you believe that this process is well established, right? Or tell me, they may say something even higher level and they may just say, tell me about the complaint, your complaint handling process, right? And so right away you have that opportunity to start to talk about something. And I always tell clients who are preparing for an FDA inspection to right off
06:51 – 07:27
Vincent Cafiso: the bat when you get those open ended questions, tell me about something, is to not say I think or not to say another 1, which is partially as part of the, I think category is when you say usually, or sometimes, or for the most part, we do this, right? We don’t, it’s not always, right? You have to basically indicate this confidence and this consistency of, of your practice. And so as I mentioned, when I’m coaching clients, I’m telling them to start out with, well, you asked me about the complaint handling procedure, that’s a process that we
07:28 – 07:56
Vincent Cafiso: that we have, which is very important to us, very important to our business. And so let’s start with the procedure and then we can kind of go from there. And so I can take you through the procedure and then we can answer your questions that you might have about the process, right? So as opposed to starting out with, well, I think this is an area that we really feel like we can do better on or something like that, right? You’re trying to sort of divert the traffic away from your thoughts, but you’re trying to bring the
07:56 – 08:05
Vincent Cafiso: traffic directly to the process, to the procedure, and to the expert people that you have operating that process on a day-to-day basis.
08:07 – 08:43
Yan Kugel: Right, so what are the best practices when you’re really unsure about something you don’t wanna guess? So 1 thing that you mentioned was a very smart way in saying, you know what, I don’t want to say anything from top of my head because usually, as you know, we work with SOPs. So let’s go to the SOP and we go through to this because this is the way we work anyways, always with SOPs, right? That way it doesn’t matter if you remember or not, because as a professional in NGMP, medical devices, you should always work with the
08:43 – 08:52
Yan Kugel: SOP in front of you. It’s not about remembering, right? That’s how you do mistakes, right? So what other ways would you think are there, if any?
08:54 – 09:34
Vincent Cafiso: Yeah, no, and there’s definitely no question that you’re going to get a question that you’re not sure about. And that’s just the nature of the complexity of what we do in quality or what we do in any of these areas that FDA would be questioning about, right? So design and production, inspection, right? There’s a lot of complicated processes and they are governed by procedures, by lower level work instructions and different other processes. And so anytime you get a question that you don’t know, which again will be probably more than half the time, right? Just because there’s
09:34 – 10:12
Vincent Cafiso: so many processes and you cannot, if you’re being interviewed as the SME, maybe you have a little bit more knowledge about the area that you’re being interviewed about. But if you are more of a manager or a director of a particular area, you might not have the exact specifics on a particular area that you’re being questioned about. So certainly, the best approach to any question is, especially if you’re not 100% sure about the answer to that question, is to say, well, that’s a great question, Mr. Or Mrs. Investigator. I am fairly certain I know the answer
10:12 – 10:48
Vincent Cafiso: to that, or at least I have an expert who can help us with that answer. And so let’s start with the procedure. And in the meantime, I’ll be following up on that question as soon as possible. I will get you that answer. So you’re not stalling. You’re just waiting to get the right answer from either the SME or by reviewing the procedure. And that’s the best way to handle any question that you’re not sure about. Even, and sorry, even if you are 100% positive that you know the answer, you can certainly say, that is a great
10:48 – 11:17
Vincent Cafiso: question, let me find out the answer to that question and I will get back to you as soon as possible. That gives you a little bit of time to prepare, a little bit of time to breathe, a little bit of time to make sure that you are exactly 100% knowledgeable about that question. And then you’re able to go back in with a fresh feeling of confidence and knowledge for that particular area, because you may have gone out of the inspection room and you may have read that particular area of the procedure. And then you can kind
11:17 – 11:23
Vincent Cafiso: of go back in and then with that calmness, go back in and answer that question.
11:25 – 12:10
Yan Kugel: Right. So step back, say, even if you think you know it, it is basically a good strategy. So I know that companies also teach people on the ground and the employees how to stall time. There are some people who are professional time stallers. So I think that the FDA and very experienced auditors also know how to catch those techniques. And it shouldn’t be overused. So you should Use it only when you really need it to take your time. Because otherwise, if you do it for every question, every SOP, it won’t be seen lightly.
12:12 – 12:47
Vincent Cafiso: Yeah, exactly. That’s a great point, Yan. There are certain areas where the question is fairly simple, like, do you have a procedure for something? Yes, of course we do, right? You shouldn’t have to go back and research that 1. And so yeah, there are certain questions where you have to be able to answer relatively quickly in order to just keep the inspection moving. If it is a domestic inspection, and by domestic I mean here in the United States, there’s a little bit more time and maybe the investigator will have a little bit more patience to allow
12:47 – 13:19
Vincent Cafiso: the firm to say, well, that’s a great question. Let me get the answers to that for you and I will get right back here. If it is a foreign inspection, those are generally only going to be about 4 days, maybe 4 and a half days. Investigators don’t have a whole lot of time. So when they start to ask questions and they start to get a build up of, I’ll get back to you kind of responses, then they start to get a little bit impatient because they just have questions that they have to get answers to. And
13:19 – 13:43
Vincent Cafiso: so you have to be mindful of that. Like you said, you have to kind of know when to be able to give a quick and decisive and truthful answer. And then other instances where you feel like you have to just do a little bit of research or maybe you just need to call in the right subject matter expert and they may be working on something right and the investigator would expect that is the case and so there’s a balance there.
13:45 – 14:25
Yan Kugel: Sure. Right. So another thing that you were talking about on this post is something that is quite blunt is saying and telling the investigator you’re wrong, dismissing the findings and telling the investigator that they have no idea what they’re talking about. So it sounds very, you know, direct aggressive. And I also have seen this happening also on some occasions. So what are the consequences when you speak in such a way to an FDA investigator?
14:27 – 15:01
Vincent Cafiso: Right, right. Yeah. Well, Investigators are human, right? They are coming in with some expertise, right? They’re coming in with their level of training. They’re coming in with their level of knowledge of the regulations. They don’t know your quality system as well as you do. And maybe they know the regulations a little bit better than you do, right? They’re coming in with their strength. They’re also coming in with possibly their own comfort zone of what they really like to focus on. So you may have an investigator who’s really comfortable in process validation. You may have an investigator
15:01 – 15:40
Vincent Cafiso: who is more comfortable in environmental monitoring or in design controls or in post-market surveillance and complaint handling and MDR reporting. Right? So you have to kind of know the investigator and you have to know what their skill set is. And part of that would be that when they are questioning or maybe they may even be using a tactic to say something that they may believe is not entirely true. So you have to think about the inspection as not always exactly face value what you think it is. Right? And so the investigator may be using a tactic
15:40 – 16:21
Vincent Cafiso: and may be asking you questions or may be making statements based on what he or she has heard that may not be entirely true. And they may know that that is not entirely true and they may be looking to see what kind of a reaction they get. And so, again, being calm and being methodical and thoughtful about your responses is very true. Not allowing emotion to get into the situation. And certainly if the investigator is saying something that you believe to be completely false, especially if they’re leading toward, well, this is definitely a nonconformity. This is
16:21 – 16:52
Vincent Cafiso: definitely a 483. I believe that this is going to be an inspectional observation, right? If they start to kind of go that way, you’re going to start to get nervous for sure. And you may even panic and you may even just get a little bit emotional, like I said. So try to avoid that at all costs. If you believe that the investigator is wrong, don’t say that they are wrong. Say, you know, I hear you. I understand the position that you’re taking at this time, it’s probably on me. I probably didn’t give you enough information. So
16:52 – 17:27
Vincent Cafiso: let me try to help you understand a little bit better what we’re doing and then see if that’s successful, right? Say, Well, let’s put a pin in that. You could always kind of use that tactic to say, I hear what you’re saying. I have somebody actually doing a little bit of research outside of here because I believe that we have the data that you’re requesting. I just, we haven’t gotten to it yet. I apologize. It’s archived off site or it is somewhere that we have to access it. So you can always respond in a way that
17:27 – 18:07
Vincent Cafiso: makes them know that you’re still researching this particular area or this particular line of questioning. And so it’s not the best tactic to say you’re wrong or to say anything like that, but it’s certainly a good tactic to say that you’re researching this particular topic because you don’t believe that you’ve given them everything that you have to justify or to support compliance. And so I’ve seen that work. I’ve seen that work. And again, it could be a tactic from the investigator to see what it is you’ll respond with. Again, it could be that it is a
18:07 – 18:38
Vincent Cafiso: short timeframe foreign inspection, and they just have to move on, right? So if they’ve gotten to a point in the day where they’ve asked enough questions on the same topic and haven’t gotten the answers that they’re looking for, they will essentially stop that particular line of questioning right up there at 43 and move on to the next area. So it is your job to know what potentially the issues are. And then this way you can hope to get them the answers that they need by the end of that day. You don’t wanna wait until the end
18:38 – 19:09
Vincent Cafiso: of the day where they’re about to issue a 483 to say, oh, by the way, we have this document you were looking for. We were kind of waiting till the end of the day to get it to you. No, give them everything that you have as soon as you have it to let them know that you’re serious about it and that you want to hopefully get the answers that they have or get the answers that they’re looking for, rather without saying, again, without saying you’re wrong, I don’t know what you’re talking about, right? All of that,
19:09 – 19:18
Vincent Cafiso: it’s just kind of emotional and not really productive to the situation. So yeah, I would certainly take that approach.
19:19 – 20:02
Yan Kugel: Right. And something quite similar to this on your list was referencing past investigators or past audits in a negative way. So I have done audits myself. So I’m also an auditor and I do some couple of audits every year to keep myself sharp on the industry. And I have been also in a situation where I came to audit somebody and they were telling me about the stories of some very bad auditors that came to them and the way they handled this by showing this plaque on the wall where it says GMP certified and saying, you know
20:02 – 20:42
Yan Kugel: what, when they told us this, we showed them this plaque and told us, you see this certificate? Yeah, how can you tell us something like this as we were certified by this and this body, right? So it already, It’s a bit already like passive aggressive, like they’re telling you, okay, you should be nice to us. Otherwise, let me show you how we handle other auditors. So at the beginning, usually when you start an audit, everybody are super nice. And usually all the audits that I do are great until you sit at the end and start talking
20:42 – 21:08
Yan Kugel: about the findings under, and suddenly everybody getting very defensive, right? But this something that I also encountered, right? Talking about, you know, past negative audits and inspectors. So what is your point of view? What is the, How can this impact the auditor and the investigator and make it less comfortable from your perspective?
21:10 – 21:34
Vincent Cafiso: Yeah, yeah. Yeah, this sort of comes off of the last 1 that we just talked about, right? Where that 1 we talked about was where you’re going to say, you know, you’re wrong, or, you know, you don’t know what you’re talking about, right? This is a sort of similar version of that, right? Where you’re going to say, well, you know, during the last inspection, you know, the last investigator that we had here, you know, They saw the same thing and they didn’t put it on a 43. They thought it was good. Like what’s your problem? Why
21:34 – 22:15
Vincent Cafiso: don’t you why aren’t you as smart as them right? You’re kind of kind of implying that Or you know, that’s where you’re putting the previous investigator maybe on a pedestal or on the flip side, you can basically try to call into question the expertise of the previous investigator, right? Or saying that the last investigator didn’t know what they were doing. And so chances are, well, it depends on where you are and where the investigator is coming from, right? So you have to know, like, if your investigator came from a particular district office and the previous 1,
22:15 – 22:49
Vincent Cafiso: and the current 1 is roughly from, you know, is from the same district office, then you have to assume that they’re friends or that they have at least had the same training and that they are fairly, you know, fairly close in terms of knowing each other. And so you would never want to say anything negative about an investigator, especially an investigator that they might know. But also just in general, you don’t want to make any disparaging remarks about anyone that works at FDA, you know, even if you’re in the midst of a pre-market application or a
22:49 – 23:25
Vincent Cafiso: 510k clearance, where you start to talk about the fact that you’re dealing with people at the center and they don’t know what they’re doing. And I’ve had just such bad experiences and I don’t know what is going on at FDA, right? It’s not like the FDA was 10 years ago. It seems like it’s really gone downhill, right? You never really want to get into that kind of a discussion or anything like that. It’s just completely professional, you know, be present, be completely 100% with the investigator that you’re with and not comparing them to anyone and not
23:25 – 24:10
Vincent Cafiso: making any disparaging remarks about the agency. Whether or not you actually have that experience is a separate story. Don’t let that taint your view of the agency. The agency is very, very big, many, many different departments and very many different centers and divisions and so different offices. And so all of these different parts of the FDA might operate slightly differently. They might have different training. They might have different ways that they go about interacting with people in industry. And so again, don’t want to compare and don’t want to make the current investigator that you’re with feel
24:11 – 24:47
Vincent Cafiso: either as if they’re superior to other parts of the agency or if they are inferior to other parts of the agency. And certainly when you’re going through an inspection, you don’t want to ever say anything even about the fact that you have an ISO certification or some sort of a previous external inspection or an external in all through and how that has gone so perfectly well and you don’t know how this FDA inspection could be going so poorly because you’ve had so many other great reviews. That is really not applicable or not appropriate for any of
24:47 – 25:25
Vincent Cafiso: the discussions with an investigator. So yeah, those are definitely topics that I’ve seen and certainly even as you mentioned, Yan, in my work where I am doing mock FDA inspections And I do get this sort of, sometimes I get this general attitude that, well, you know, we’ve had notified body audits, we’ve never had a problem, we’ve never even had a minor finding, let alone a major finding. So this should be a pretty easy mock inspection for you. And it’s almost like, if you say that to me, or if you say that to an investigator, it’s like,
25:25 – 25:48
Vincent Cafiso: you know, challenge accepted. Now I’m really going to dig in, and I’m really going to find something to let you know that you should not be feeling so confident during inspections. And so I wouldn’t want to do that. It’s definitely a challenge to an investigator if you tell them that you’ve never had a problem, you’ve never had a finding, you’ve never had a nonconformity, you’ve never had a 483. It’s just not a good way to go.
25:49 – 26:32
Yan Kugel: Right. So basically, if an investigator didn’t have a finding, he probably didn’t dig enough, right? So there is no such thing. And I also hear it that companies are very quickly becoming very comfortable. And I see it happening when, especially in big pharma, where they are getting audited, but the same people every year in the same zone and area, So they get the same people and they get acquainted. The same person always looks the same place. They’re probably after so many years on a friendly note. And then suddenly the inspector changes or somebody else comes and
26:32 – 27:16
Yan Kugel: they have a different perspective, they start looking into different directions, suddenly the critical findings come out and You see it in so many companies. It doesn’t matter if it’s such giants, right? We’ve seen it as well with Pfizer during the COVID, right? So it doesn’t matter how big you are and how comfortable you are, the more dangerous it becomes if you just stand still and doesn’t continue improving your system because for sure something is outdated and something was missed. So you should never be so comfortable and confident that, yeah, you know what, our system is just
27:16 – 27:19
Yan Kugel: perfect. There are no cricks.
27:19 – 27:55
Vincent Cafiso: Right? Right. Yeah. No, exactly. And it actually, as you mentioned, some people who are being audited or who are being inspected, they may have a comfort level and they may almost let down their guard a little, right? So they may actually start to kind of meander toward the, you know, where it becomes a little bit informal and they start to, you know, and it’s okay to talk to an investigator about whether or not they had a good ride in, right? Did you have a good commute? Was it okay? Did you get here safely, right? Or, wow,
27:55 – 28:28
Vincent Cafiso: I don’t like traffic. What about you? Do you like traffic? It’s easy to have those connections. And you may be kind of lower the temperature in the room a little when you start to kind of get into those, especially when you’re in maybe middle of the day, or like, as the end of the day gets in here, and we’re starting to get into some issues, right? It’s okay to do that, but you never want to get into those questions where, not questions, but situations where you start to say, well, the real issue is that we just
28:28 – 29:01
Vincent Cafiso: don’t have enough people, right? Or where you start to have that comfort level with the investigator, which is okay, but you just don’t wanna let your guard down to the point where you’re starting to give information or give sort of informal, like there’s nothing off the record, right? There’s no such thing as off the record during an FDA inspection. So anything that you say to the investigator is going to be taken in and they’re going to be thinking about it. Like, well, you know, if you’re going to say, well, you know, probably shouldn’t tell you this,
29:01 – 29:30
Vincent Cafiso: but right, that’s another 1 of those where you’re kind of letting your guard down. And so you have to be careful. You can still build rapport and you can still have a good relationship and you can still make a little bit of small talk and try to find some common ground about, you know, where you went to college or whether or not you grew up in the same state or the same area or whether or not you have family that lives where they live or something like that. That’s okay, but don’t let it bring you down
29:30 – 29:41
Vincent Cafiso: to the point where you’re going to start to be a little bit too comfortable, where you’re going to start to tell them things that you wouldn’t really want them to know about the company or about the position that you’re in from a compliance standpoint.
29:44 – 30:14
Yan Kugel: And as the investigator, right, So you have a lot of training on the best practices of auditing and psychology, et cetera, et cetera. So is there also some kind of training on, befriend and try to get the people there to open up in such a friendly ways. Is it part of the training also to try to be on a very friendly way?
30:15 – 30:58
Vincent Cafiso: It is. I mean, I think that’s a way to gather some early rapport and some early trust as an investigator with the host or with the auditee, the person who’s answering the questions. And especially as you see sometimes new SMEs come in, right, and you can see that they’re coming in because they know that they have to answer questions and they may be actually anxious about it. And you could tell that there’s that anxiety in there. And so I know that if I want to get the best performance out of that SME, I’m going to try
30:58 – 31:29
Vincent Cafiso: to relax them. So that is part of it where I may make a joke or I may say something that makes them feel a little bit more comfortable or I may even tell them, say like, you look a little bit nervous or you look a little bit anxious. Do you want to just take a few minutes to take a deep breath? Did you have lunch yet? Did you have coffee? Do you like coffee? Right? You know, something like that where you might say, well, let’s just take a deep breath, let’s slow down, let’s relax. And then
31:29 – 32:02
Vincent Cafiso: you can sort of start to get and again, if they’re recognizing that you recognized, you know, that they’re that they’re a little bit anxious, and that you took the time to relax them, they might feel, well, okay, this person’s on my side, at least I can now explain to them what it is. And of course, they should still be factual and they should still say, well, I’m not sure that’s a great question. Let’s look at the procedure, right? They shouldn’t be using, you know, so it’s really just a matter of trying to get the person to
32:02 – 32:37
Vincent Cafiso: relax, to calm down, to give the information that you’re looking for. And that’s part of the coaching that I do here with the clients at Creio is to let them know it’s okay to come in and be anxious. That’s okay, but we’re gonna try to give you some tools to relax and again, a lot of that comes from, a lot of the anxiety I’ve found sometimes comes from the feeling that they’re not sure what to say, or they’re not sure how to say it, or they’re not sure how to start, right? So we always try to
32:37 – 33:10
Vincent Cafiso: start with the procedure, start with the process, and then we start to work our way into the issues, right? We have known issues that we believe will come out during the inspection, right? So that’s where we get into that next level of it, where we’re gonna present top level. Here’s our quality manual, right? Here’s our top level documentation. We’re gonna get into the SOP, the standard operating procedure. And then we’re gonna get finally into the application and how do we implement that process. And then, of course, the investigator is going to get to what are the
33:10 – 33:43
Vincent Cafiso: issues, right? If we’re talking about complaint handling, if we’re talking about dealing with production deviations, right, How are we handling those? Let me see a list. Let me see the last 2 years of deviations, right? So now we’re gonna actually get into the records and eventually the investigator is going to find some of the high level or some of the key issues that have been happening. And so that’s really, I think, where the SME already has that anxiety because they don’t want to get to that level, get to that place. They don’t want to have to
33:43 – 34:14
Vincent Cafiso: talk about that particular area because they know that there’s a weakness there. And so, again, I think that’s when an SME comes in nervous, it could be either that they are just nervous, they’re just generally nervous person because they know that they’re talking to an investigator and that’s happens every day. Or it could be that they are preparing for what they know eventually we will get to which is the issues and how we’ve dealt with the issues, and how we’re going to make sure that these issues don’t ever happen again. Right. And that’s, I think, where
34:14 – 34:25
Vincent Cafiso: a lot of firms start to feel a little bit anxious about, not the day to day, but how have we dealt with the issues that we know have happened and how we’re going to be able to present those during an inspection.
34:26 – 35:18
Yan Kugel: Right. Yeah. So those are valid points. And another thing that you mentioned on your list, and this is something that I also have through my posts of the most dangerous words or phrases in the pharma industry. And 1 of the most dangerous phrases in the English language is also the classic, we have always done it this way, right? And this is really classic. And because you wrote it, I understand that this comment that you still hear it a lot. And so what is your approach to this kind of a comeback? We all have always done it
35:18 – 35:36
Yan Kugel: like this. And why do companies still keep saying this? I would have thought that they already pass this with understanding that continuous improvement is needed, but it feels it’s not the reality. So what is the reason for that?
35:36 – 36:22
Vincent Cafiso: Right. Yeah, I think it’s definitely that limited mindset, right, where they feel like what they’ve been doing so far has worked. It’s maybe gotten them to where they are. But a lot of times in life, not just in medical device or pharmaceutical production or any sort of the processes, right? What got you here will not get you there. And so sometimes when companies don’t have this mindset, they are very protective too. I think you have a lot of situations where you may have somebody who was the creator of a particular process or may just have some
36:22 – 37:02
Vincent Cafiso: sort of a personal connection to a particular process. And so they may feel like they’re being personally attacked when you start to ask questions or when you start to poke on something. And so certainly when you want to go there, when you want to start to ask questions and they start to feel very defensive, that fixed mindset is something that you can tell. And 1 thing, you know, as an investigator, especially, you know, it depends on where you are an investigator, at least where I was an investigator, there was a lot of industry, a lot of
37:02 – 37:45
Vincent Cafiso: industry. And so I was doing inspections of not only multiple types of companies, doing different things, different applications, different dosage forms, different device types, but also I was going to the same type of company, literally competitors of other companies that I was also inspecting. And so you can actually start to build up a little bit of an inventory of how to do something in a way that you believe is probably the best way to do it, right? Because you know, you’re just benchmarking from company to company to company that are doing the same thing. And so
37:45 – 38:17
Vincent Cafiso: when you go into a company that may not, at least in your opinion as the investigator, right? You see that it has been done maybe other ways and definitely maybe other ways that are better than what you’re seeing currently. You start to maybe ask questions about, you know, what led them to decide that this was the best way to do it. Again, as an investigator, knowing like there are many other ways that you have seen that you believe are happening better, where they are resulting in fewer deviations, fewer nonconformances, fewer CAPAs, fewer complaints, right? So you’ve
38:17 – 38:48
Vincent Cafiso: seen companies that are doing things better. And then when you go to a company that you believe has, you know, from the data, right? Not your belief, but you know, as an investigator, you’re looking at the data, right? How many deviations, how many non-conformances, how many in process failures, how many product, you know, release, pre-release failures. Right? And so you can see that if a company is struggling, you start to ask them questions, you know, and if you are astute, you know, at hearing what the investigator is getting at, you may realize that they’re actually trying
38:48 – 39:26
Vincent Cafiso: to help you. And that was actually 1 of the reasons why I felt like it was my time to go and move into industry after being an investigator for all those years was because I really wanted to start to help. I really started to feel like I had pointed out problems for long enough and that I wanted to really fix problems. And so investigators may be on that part of their journey too, where they’ve seen things happening so many times. And they are their mission. And even to this day, my mission is to protect the public.
39:26 – 39:57
Vincent Cafiso: And so if they see something that’s happening where they believe it can be happening a little bit better, They’re going to start to ask questions now. Of course, they cannot consult, but they may ask questions like, hey, why are you not doing it? You know, using an automated tool or why are you doing it manually? Have you considered automated options? It’s because they’ve already seen it done many, many times that way. And they’ve not maybe seen many companies doing it manually or, you know, whatever the example is. And so if you get questions like that from
39:57 – 40:26
Vincent Cafiso: an investigator, it’s usually because they’re coming from a place of wanting to help and wanting to make it better, but they just can’t actually tell you how to do it. They just have to ask you the questions and ask you, like, if you’d consider doing it this way, to see if you’ll kind of latch on. And they may even, you know, if you do latch on, and if you do start to receive those questions, you may actually get the investigator to open up and to give you maybe a couple of names of tools that they’ve seen
40:26 – 40:32
Vincent Cafiso: that work really well or other people that they could talk to that have done it better. So yeah.
40:33 – 41:14
Yan Kugel: Right. So it connects also very well to the first point of telling the investigator that they have no idea what they’re talking about and they don’t know what’s going on, They know it best. So they sometimes forget that the professional auditors and investigators, they go out and audit dozens, hundreds of companies. So they have seen so much, right? And A lot of professionals also in big companies, they usually a lot of time work in the same company for 20, 30 years. So usually they know how things are going in this company, but they have a blind
41:14 – 41:54
Yan Kugel: eye for some processes. So they just, they have the curtains across their own, they don’t for some processes, right? So they just, you know, they have the curtains, right, across their own. They don’t see the opportunities, the possibilities. And this is exactly the point where you should listen carefully, as you said. And you also mentioned that sometimes the ODTs won’t help. Okay, how should we do it? So you also mentioned that at some points, it can be also passive aggressive. So when they say, oh, so what do you suggest us to do? Right. So there is,
41:54 – 42:19
Yan Kugel: of course, this way of saying things or sometimes they’re really interested in help, right? And as an auditor, you’re not always allowed to give the advice legally as well. And that’s why they have the also in the morning letters, right, okay, we recommend taking a consultant, right?
42:20 – 42:58
Vincent Cafiso: Right, right. Yeah. And it really is, it really depends on right, so you can ask the same question almost, 1 of them would be considered not what to say, right? Like, if you say, well, what do you know, you could say, what do you suggest, right? So if you’re having a conversation and it’s a productive conversation, right? Where like you mentioned, right? They’re professionals, They’ve seen the same operation multiple times elsewhere, probably at your own competitors. And so if they start to ask you questions and they start to say, well, have you considered this? And you
42:58 – 43:35
Vincent Cafiso: say, well, hey, No, actually, we haven’t really considered this, but what would you suggest? If you approach it that way, they might say, well, as you know, we can’t consult you, but I have seen this done automated and it really is pretty neat. It seems they can start to give you a little bit, a little bit of that consulting, right. But if you’re at a point where you’re, you know, very emotional and you know, you’re feeling attacked and you, you know, you’re at that stage where they are trying to help, meaning the investigator is trying to
43:35 – 44:15
Vincent Cafiso: help, but you’re not listening or you’re not hearing it the right way, or you may feel like you’re being attacked and you can say the same words instead of saying it, well, what do you suggest? That’s, I would love that feedback. You know, when you say it kind of more inflammatory, like, what do you suggest? It’s like you’ve said the same words, but you’re saying it completely differently based on the context of the conversation that’s happening. So I would certainly, I would never recommend to say what do you suggest in an antagonistic or in an inflammatory
44:16 – 44:49
Vincent Cafiso: way. But if you can develop rapport with an investigator and you can, again, start to see that it looks like they want to help, I don’t think it’s out of bounds to ask them, what would you suggest? Or do you have a better way to do this? Because we’re all open for improvements, right? We would love to have some continuous improvement here. And that’s part of our quality policy. It’s part of our mission statement and our vision is to continuously improve to make sure that we can, in fact, make sure that we are protecting the public.
44:50 – 45:24
Vincent Cafiso: We think of our customers as our family members, and so we really want to make sure that we’re doing the best thing. So yeah, if you have any suggestions or if there’s any 1 that you think that we should reach out to or any software or something that you’ve seen that really works. I don’t think that that’s out of bounds. The investigator could say, well, it’s flattering that you would ask me, but honestly, I can’t help you. Well, you try. You’re no better or worse off. It wasn’t any sort of an inflammatory or antagonistic approach. And
45:24 – 46:01
Vincent Cafiso: so you really can go that route if you feel like you’ve got there with the investigator. Again, if you feel like the area that is the topic of what the investigator is asking you about, if you feel that there are really major compliance gaps, then you may not have that opportunity because they’re going to essentially say, well, you know, you’re going to have to research this and you’re going to have to come up with a really comprehensive, you know, response to the 43, right? If you’re at that level where, you know, the area that they’re talking
46:01 – 46:32
Vincent Cafiso: about is really off, you know, out of bounds and completely out of control, then of course they’re going to not be able to give you that. But if it’s probably more of an improvement to the process where it’s still compliant, there’s no issues with it, it’s validated, it’s not resulting in major, you know, major non-conformances or major deviations, then they would probably be more likely to work with you on at least maybe helping nudge you in the right direction. But if it’s out of compliance, I don’t think that they’re going to give you any of that
46:32 – 46:33
Vincent Cafiso: feedback.
46:35 – 47:17
Yan Kugel: Right, great. Thank you for this advice. So that’s good. And so 1 of the craziest ones that I’ve seen on the list as well, And for me, it’s like shooting yourself in the leg when you’re saying this. If we would have followed those procedures, we would have… So if you follow those procedures, we would never get anything done. Right. So basically saying something like this to an investigator that basically admitting you have procedures, but you tend not to follow them and you do it on purpose. I think this is the 1 of the most self-destructive things
47:17 – 47:55
Yan Kugel: that you can say that can just, I guess, bury you in this investigation. So in which scenarios have you heard this and what are your recommendations, you know, in such cases to companies to maintain professionalism, but also keep the efficiency that they want. But 1 thing is certain, something is wrong there in this department or company if this is happening and if this is methodic this is this can be destructive so We’re in what scenarios do you see it?
47:56 – 48:37
Vincent Cafiso: Yeah, and a lot of times I see this where a firm will have procedures that are They’re in place They are I would say Compliant right there. They’re there. They’re there. They’re in place, they’re compliant, but they’re ambiguous, right? They don’t give all the detail. And those are the firms that I can definitely see will have some inconsistencies in their practice. And so that’s really where you start to dig in because you wanna see, well, this procedure is, it’s referring to there being some sort of an amount of time that something needs to be done for.
48:38 – 49:19
Vincent Cafiso: And so I’m looking at a form where they have to record certain process parameters and time is not on the form, right? Time is not being recorded yet the procedure does refer to some timeliness element, right? Or a temperature element or some process parameter that needs to be recorded and then the output of those processes are not actually recorded or they’re recorded inconsistently. I’ve actually seen situations where you look at batch records and some batch records, again, if we’re talking about a batch record that requires some sort of a time or a temperature element to it.
49:20 – 50:01
Vincent Cafiso: And so you’ll have a batch record that doesn’t have that information recorded, but then you’ll get a different batch record and it has that information recorded, like on the back, handwritten, completely in an uncontrolled manner. And so those are the situations where you definitely know that the company is not following their procedures exactly the way that they’re written. And it’s because of probably a weak quality culture, right? They don’t have the culture of having highly skilled and highly trained individuals. They don’t have people who are really looking at the procedures to make sure that they are
50:01 – 50:35
Vincent Cafiso: clear, that they are fully describing the process. So that’s really where it’s… And I’ve seen some companies go that route. They go the route of, well, we don’t want the procedures to be super detailed because we don’t want to set up what we’ll call trip wires, right? We don’t want to set up compliance trip wires where if we have everything specifically required by the procedure and we don’t do any 1 of those, we’re out of compliance. So there is a balance to how you have to write your procedures so that they are clear, that anyone can
50:35 – 51:10
Vincent Cafiso: pick up those procedures if they are trained and they have expertise in that area, they can go ahead and pick up that process. Where you don’t want there to be this situation where you have tribal knowledge, right? Tribal knowledge meaning that you have people who have worked there for a long period of time and that they’ve developed their own little skills and their own little techniques to doing something. And that’s not really in the procedure because that’s just some process that they developed over time. And so especially if you have some technology or some scientific process
51:10 – 51:39
Vincent Cafiso: that needs to happen, and it needs to happen consistently, but it just so happens that, Well, you know, the person who’s doing it, they tend to do it on a morning. And they told me that, well, if they take the product that they’re working on and they put it on the, in the area where, where the sun hits the, where the sun hits the, it’s the desk, that’s really where they get the best results. If they tend to put that material, that in-process material somewhere else, it doesn’t always pass. So there’s some process parameters that they
51:39 – 52:13
Vincent Cafiso: haven’t fully figured out. And again, there’s this tribal knowledge and there’s a lack of procedural detail. That’s really where you start to see the inconsistencies. And it’s something that investigators are highly trained in being able to detect, right? So they’re going to go out onto the floor, they’re going to see different people doing different things. They may even go into second shift to see what is happening on second shift. And so, that’s really why the procedures need to have a level of, of detail in there. And again, it comes back to inspection readiness. And it comes
52:13 – 52:43
Vincent Cafiso: back to being comfortable to be able to hand a procedure to an investigator and saying, yeah, here’s our process. This is exactly what we do every day, all day, every week. This is what we do. All of our procedures are experts. They can do this. And that’s why we have such good consistency and good quality, right? So again, it starts with a quality culture and knowing that this is important and then making sure that the right people are in place, the resources are there and that the right reviews are happening periodically to make sure that these
52:43 – 52:45
Vincent Cafiso: things are being looked at.
52:46 – 53:33
Yan Kugel: Right, Yeah. So I’ve seen those issues in also in a couple of cases. So 1 of the cases is when a company which is in its early stages or it’s an API manufacturers and manufacturing, they want to go GMP or some smaller companies. And what they do, they bring big consultancies who input plug and play SOPs. And they don’t really reflect the what’s happening on the ground, but they just have the nice list of SOPs to make sure that they cover everything, but the SOPs are not really aligned with the real processes, right? And then the
53:33 – 53:41
Yan Kugel: problems happen during audits because of those issues. So have you seen such occasions as well?
53:42 – 54:13
Vincent Cafiso: Yeah, and that probably is something that I could say maybe in our in part 2 of this of this particular post, because I have had I have had situations where they will at some point during the inspection admit, Like they almost sort of like throw up their hands and say, well, you know what, that whole quality system came from a consultant. We really don’t follow that, right? They don’t really, they didn’t know what they were doing. They just, you know, came in and put a procedure, you know, put procedures in place and they didn’t spend time
54:13 – 54:43
Vincent Cafiso: really learning the process. And so we have to, you know, we have to kind of do things outside of the procedure. You know, that was something that we did because it was for compliance. But when we when we’re talking about making sure that we do what we need to do to produce product, yeah, you know, that’s this sort of separate process that we have. So yeah, anytime in that I’m not saying that that’s a bad thing, right, you can have a consultant come in and help you out, it depends on, you know, depending on the stage
54:43 – 55:16
Vincent Cafiso: of your of your process, you may want to start with the procedures that you need. So don’t go for the what I call plan in the can. Don’t go for the entire suite of quality system procedures, but just go for the ones that you need. So if you’re early stage, you want to have design controls, you want to have clinical suite of procedures, you may even want to have some early supplier management type procedures, right, as you get going early on in development. And then maybe change control, right, as you go. But, and then scale and
55:16 – 55:47
Vincent Cafiso: build and really perfect those procedures as you go. It’s why we have continuous improvement. That’s why we have change control. That’s why we have a change process that can scale the process and further improve it as we move along. But yeah, I know I have seen that and it’s definitely not the best way to go about presenting your quality system during an inspection that it was well, it was a consultant that gave us this quality system and we really don’t follow it.
55:47 – 56:26
Yan Kugel: Right, right. So it’s something similar to another point on your list, which is blaming predecessors or blaming other people for the issue and said, oh, it’s not me. Somebody did it like 5 years ago before I came and then it’s total chaos and that’s very similar I think, right? Yeah, so, so Denise is right. So I think we maybe covered 50% of it. We can sit here all day and discuss every examples for each, but it’s a really great. So I think on this note, we will wrap it up and we might continue this nice chat
56:26 – 57:02
Yan Kugel: on another episode. So Vincent, thank you very much for this chat. Again, I will remind that you can connect with Vincent on LinkedIn. You will see the link to his profile in the description of this episode. So go there, follow Vincent. If you have any questions, he would love to connect with you. And again, Vincent, the director of quality and compliance at Creo, great talking to you today. Thank you.
57:02 – 57:06
Vincent Cafiso: Yeah, no, your honor, it was my pleasure. It’s always fun to have these kinds of conversations.
57:07 – 57:10
Yan Kugel: Great. So thank you very much and see you in the next 1.
57:10 – 57:11
Vincent Cafiso: Thank you.
57:31 – 57:32
Yan Kugel: you
Yan Kugel is joined by Mohamed Amer, a seasoned executive with over 20 years of experience in strategic and commercial leadership in the healthcare industry. Mohamed emphasizes the significance of […]
