Darshan
Hey everyone, welcome to another episode of DarshanTalks. I'm your host Darshan Kulkarni. It's my mission to help you trust the products you depend on. As you know, I'm an attorney, I'm a pharmacist and advise companies with FDA regulated products. So if you're thinking about drugs, wonder about medical devices or obsessive pharmacy, this is the podcast for you. I do have a special specify. I'm an attorney, but I'm not your attorney. I'm a pharmacist, but I'm not your pharmacist. So this is neither clinical advice, nor legal advice. I do these podcasts because they're well on live streams, because they're a lot of fun. And I find myself learning something new every single time. But it's nice to know someone's actually listening. So if you like what you hear, please like leave a comment, please subscribe. If you want to find me. Reach out to me on twitter at DarshanTalks or just go to our website at DarshanTalks calm. I do also want to emphasize that if you like the questions we're having, and you'd like the interaction we're having, please, please, please ask questions. Also, if you like the conversation, please do share it. We appreciate that. So kind of getting to today's point, our our guest today is is going to be helping us discuss. And this is the plan as we speak, I expect it's going to evolve as we continue. But our goal today is really talking a little bit about FDA engagement. And if you are in any FDA regular space, you know how scary that can be. So if you are interested in finding out how do how do companies, how do individuals interact with the FDA? What are the concerns? What are the How do you plan for that, you probably want to listen into today's conversation. Our guest today is the SVP of global Regulatory Affairs quality and operational excellence at Ciro's pharmaceuticals, we've had him on multiple times before, he is absolutely fascinating to talk to because we learned apart from everything from Regulatory Affairs, to operational excellence and and what that actually means. And we it's been a pleasure having you on as a guest multiple times before. I'm excited for today. So our guests today, Ashley Preston. Hey, Ashley.
Ashley
Good morning. Thank you for having me. Again, it's always
Darshan
thank you for coming on I as we discussed earlier, you did get the memo about all of us wearing the same shirt and doing the during the beard with the mustache thing. So it's good to have you on. Um, one of the things we were talking about as you're getting on is you were starting to have discussions with the FDA, and I'm sure that's the constant state for you anyways, but let's let's talk a little bit about when and how to engage with the FDA. If you are if you have a new potential product, when do you start planning? What is the appropriate time to start engaging with the FDA? What are the appropriate milestones to get into? And let's kind of go from there.
Ashley
Sure, absolutely. So I think it's the the number one rule is engage early and engage as frequently as is as as possible and as is reasonable. But it's important also to make sure that you get the maximum maximum benefit, if you'd like out of your engagement. So it's I always I always take the rule that we don't have a meeting with FDA for the sake of achieving a meeting, but we want to achieve a specific outcome from that meeting. And we only call that meeting when we know we can have the data available to justify our position. Because typically it's a it's a q&a. So we are making proposals, asking FDA whether they agree to what we're proposing in our development program, and looking for alignment with them on that and also advice if they you know, agree or disagree, really, they will still provide some advice as to them, like shape your, your program. So key to that is having the data available to really properly support that justification. And that will get you the best outcome. So aligning your meeting around the availability of that data. Now, we think about the earliest possible opportunity really, that biologic comes with the pre ind meeting. So once you have a drug candidate identified, you know it has some, you know, activity, you know, in non clinical studies and you are embarking on your ind enabling GLP tox studies such that you can file your ind, it's always good practice to file for a pre ind meeting with FDA to make sure that you cover up any questions you might have around your ind the content of that ind when the studies that may they may expect to see any particular nuances around your product that you're concerned about or that you want to cover off with FDA that then enables them to make more informed review of your of your file and also avoids that that lag time if you like where if you if you don't have your pre ID and you're not aligned on some of these topics, then they will come questions during your ind review. And that is typically a crunch timeline because as you know, FDA for an ind has a statutory timeline of 30 days for their to review and make an objection to your your submission or give you a safe to proceed letter. So you know, that can be that can be a time crunch. So it makes a lot of sense for companies to approach FDA for the pre ind stage, make sure they're aligned as much as possible for their their ind, and then one that when it comes to filing, it's a much easier process and a much smoother sort of pathway to acceptance of that ind and opening your your Phase One study.
Darshan
So so we're talking about this pre ind phase, and we're talking about, as you put it, meet as early as possible, be as often as possible, so that you're, you're always going in the same direction. The two questions that come to mind for me is number one, this, this idea of during COVID, the FDA has been very, very busy. And the question is, how do you get the FDA attention to give you those meetings? And have you seen delays?
Ashley
Right, so I think I think the Euro, the COVID, has put a absolutely, absolutely COVID has put a strain on if there's resources and I think that strain was it's felt across the board at FDA, it's more acutely felt in particular divisions. Obviously, things I can divide the antivirus division and cdrh is really, you know, stretched thin at the moment, and probably will continue to be for the foreseeable future, because there's so much activity happening in the COVID space for diagnostics as well as therapeutics. So but in in thinking about preparing for your meeting, when you when you file your meeting requests, you are required to lay out your questions and rationale for why you're asking those questions so that FDA can make an assessment of the type of meeting that can be granted, clearly, during COVID times, you know, face to face meetings are not happening, not that I'm aware of. And so it's almost a strategic point to not even not even worry about asking for a face to face meeting and go straight in asking for a teleconference. Because the three options really a face to face meeting a teleconference or written responses only at FDA will make an assessment based on your meeting request as to what type of meeting can most appropriately address your concerns at that time. And that that is dependent upon the stage you are in, in development, but also upon the the criticality, if you like of your of your questions, and whether they view that there is some need for for a discussion around those topics. Or if they're very straightforward, you're they may issue you a meeting that is written responses only. And at that point, you put in your briefing book, everything you have in terms of their content, you won't have a dialogue with FDA, they will they will give you their responses, and then you take those and you move forward. But ideally, if you can get some dialogue with them. So the experience we've had is, is that simply being as as comprehensive as possible in the meeting request to help FDA to understand the criticality of your of the questions you want to ask and the topics you want to discuss. And then we have we have simply gone for applying for teleconference, because it makes it also a lot easier logistically for FDA to accommodate that they are also you know, have some level of remote working happening. And so that seems to be very, you know, any a much easier path to getting that discussion. And we've we've had that several times over the past sort of year and a half, two years, and it's worked quite well.
Darshan
So what do you think, obviously the advantages of a teleconference is number one, the FDA is more eager to grant them, do you? Do you feel like you are getting more meetings? Or does it? Does it feel like you aren't getting those same number of meetings? It's basically it's just business as usual, just teleconference, for the most part.
Ashley
At the moment, yes, it certainly in my experience, I know it can also vary amongst division. So it's Eros we working with the oncology division and, you know, they, as a division, you know, I would have to say leading the way in terms of in terms of expediting drug development, streamlining drug development, and also interactions with with sponsors, so, we have not seen any delays, but I do understand that they, you know, due to resource constraints, there have been some delays across the board, you know, for for industry meetings, but, you know, we've maybe perhaps we've been lucky in that regard. And I find it the teleconference, I don't I don't find it any less effective than the face to face meeting because you still, really the key is being able to have that discussion. You submit your briefing book with your your questions, and your your justification for for your proposals, you get your preliminary feedback, and then you're able to refine that down to the questions that you want to specifically discuss with FDA. And it can be very important to, to have the opportunity to step FDA, the FDA team through the details of what you what you're trying to convey, not all of that can necessarily come across in a briefing book in a written form. And having that back and forth discussion, being able to, to sort of modulate on the fly, you know, if something is you know, they have a concern about a particular area, you can have your expert there, too, to discuss in a little more detail and, and sort of be be flexible in how the discussion is, is handled and how that evolves. And by and large, you know, I think it's, it's, it's definitely a positive because you can then really fully understand the perspective of the reviewers. They get to also understand your perspective, bit of back and forth negotiation and come out to hopefully, what is a win win scenario for for your development program, and ultimately, for patients.
Darshan
So you talk about the importance of the teleconference, let me ask a really basic question. My experience with the FDA, generally speaking, is that they don't like to be held too closely to what they're saying, because they're often sort of helping it's a conversation, it's a it's a discussion, can you record the conference, or does it have to be sort of unrecorded, and then you have your meeting minutes?
Ashley
Yes, it's it's unrecorded, it's and but it's the agreements are captured in the meeting minutes. And that's where part of part of that discussion process is to really to have the discussion on the topic and and, you know, a line, you know, between us and the FDA reviewers, on what the what the outcome should be of that particular question. And then it's important for for the regulatory folks in in, in the industry who are managing these interactions, to make sure that you also reiterate that and it's clear to everybody before you move on to the next topic, what what should be reflected in the minutes, what we all believe is, is the outcome of this discussion. And be clear about that. And if you have to repeat it, repeat it, because it's better to take that time and everybody be clear then to have some ambiguity, and try and play catch up later on. Now, not everything is is necessarily always captured completely as everyone understands it, when the minutes come out, because it's, you know, everybody's human. And we, you know, we, you know, that happens. But again, we do that, and when you receive your minutes you review, you make sure that you that it's consistent with what your understanding of the outcome of the meeting was, and you have the opportunity to to discuss with your FDA project manager, if you do see something that doesn't match up with your takeaway from the meeting. And you can, you can have that negotiation with them as well, they can, they can engage the review team, and make sure that that what is reflected in those final set of minutes is agreed upon, you're amongst the, amongst the FTA review team and the sponsor, that that was the outcome. Now you might not necessarily always agree with the outcome. But that, you know, is the outcome of the meeting and their advice on that.
Darshan
So So speaking of that, speaking of this idea that you're having this discussion, the meeting minutes may not necessarily always reflect what you understood. Do you think it's a good idea to take meeting minutes and share that screen, especially since you have the opportunity during the teleconference so that they're seeing exactly what what you think you're hearing? Or do you? Do you think that's gauche?
Ashley
No, actually, we've had we've so we've had the experience, I've had the experience, both ways. So I think it became a little more difficult during COVID, because of the just the logistics of connecting the reviewers if they are remote themselves and into your into your call. But pre COVID, we also had the experience with it with a pre ind where the focus of the meeting was actually the the meeting minutes draft were projected during the meeting. And our FDA project manager went through and actually wrote the meeting wrote the draft of the minutes as we were agreeing on each of the topics, and we were able to then have that interaction in real time. And that that was, you know, biologic, a better way to go. But understanding that it's more challenging, you know, in the COVID times when we're not everybody necessarily at either end is in the same room.
Darshan
So So, but but you don't think that a teleconference gives you a better opportunity to do that? Or do you think that and then sort of raises the second question, but I'll wait for that second question. What you described is they're projecting it in a live screen so that you're all in the same room to seeing the information being written out. I would think that that works even better if I'm using a zoom meeting, or it's using something like that, because it becomes advantageous because you get to see you get to share this screen technologically. Or do you think that at a practical level, you're showing data and that screen is already being used as just not feasible to be jumping across multiple screen at the same time?
Ashley
No, I agree with you, it's having having the draft minutes projected in real time and being able to have the discussion on a topic, present your data and then agree on what will be reflected in those minutes in real time is absolutely the best outcome. But it just as it turns out the to do that, then you have to have both groups of people, particularly if FDA are projecting the screen, you know, they are wanting to be in the same place at, you know, at down in Maryland, so, and during COVID times, it's not always possible. So I think that it's been a little bit more about a verbal connection onto the, onto the teleconference itself, rather than having the opportunity to project. But hopefully that will, we'll get back to that, you know, very soon. And that is absolutely the optimal outcome in my mind, if you can't get a face to face meeting.
Darshan
So let's ask the question that goes along with this, which is there obviously three different methods, the and you mentioned a few seconds ago, a real time meeting teleconference and a written response, the written response, the advantages that you get it in writing, you have exactly what the FDS perspective is, they can hedge it all the way they want, but you know exactly what they're thinking and it's there in black and white. If you are choosing in, say, two years, would you choose a teleconference? What are the advantages and disadvantages to that? versus a live meeting? Do you think it gives you more opportunities, less opportunities? And what do you gain by doing a live meeting that you can't in a conference?
Ashley
To be honest, I don't see a lot of advantages, necessarily in a live meeting. Oh, that's interesting. The disadvantages of you know of the logistics of traveling, so what I mean, it's other than being face to face with the reviewers, and that, that sort of personal sort of rapport, if you like, if you if you're there often enough to build up with them. But I think you can still get that on video, I think I think the world has shown now during a pandemic that we can operate, you know, we can have interactions like you and I having now you know, via video, and it can be productive and effective. So and I think it's, it's, to me seems far easier in terms of managing the logistics, managing the workload on both ends, to, you know, to go this way, because I'm sure you know, FDA can can fit in your meetings, virtually, then then having to, you know, accommodate all the logistics of the face to face meetings.
Darshan
So, so one of the questions I have to ask is, I've been a part of many of these FDA audits and sort of responding to the audit and all that good stuff. And one of the things you do is you have the FDA room where you have the one person taking notes, the scribe, if you will, and then you've got a separate room all together, where you're actually doing the battle planning, and you're kind of going, FDA is asking for this, what do they actually need? Do we need to give this document if this document, does it? Does the whole thing need to go? Or is it just as an individual component, etc, etc, etc. My question for you is, that is often seen as a little bit more of an antagonistic relationship in the case of an audit, because you're trying to make sure that you're putting your best foot forward, and you're not sort of exposing everything as much as you possibly could. On the other hand, in the case of a application, and what applications and look like, I imagine it's it's, there's more of a collaborative approach. But do you do you have in the case of a teleconference, a separate room that you are going, Okay, we need this expert lined up, because the FDA may ask these questions, but we don't want to expose them until we know so that like, Is there a protocol you guys have for these conferences? Or do you do sort of go look, I've done 1000 of these, I know how to handle it.
Ashley
No, we so when we, when we get our preliminary responses from FDA, we'll take a look through and hone in on the questions that we want to address with him during the discussion, and we'll make sure that we have our experts in those areas, who can who can speak to that, that content on the call itself. And they will be available as that topic comes up to to you know, provide their input, you know, present the data, be part of the discussion with the negotiation suggest options, should we or should we be looking for alternatives? And so we have we have them available, definitely on the call because it's I think the really, to me, the role of the regulatory affairs, you know, expert in in the FDA interaction is to facilitate and manage that that discussion to make sure that that from an overall regulatory perspective, we have what we need to be able to move forward and execute on the strategy but we always I mean, drug development is a team a team game and always will be and so we, we absolutely rely on the expertise of our SMEs in a given area, to provide that, that content that we can then, you know, whether it's a meeting or crafting a submission, you know, regulatory will help to synthesize the data and craft, the craft the narrative craft the story of, of the drug such that it is persuasive for, for the submission or for that discussion.
Darshan
So, which, which obviously speaks to the idea of having people available, but but how do you address the question of who does the talking? Who decides? Whether we're going to bring this expert in this moment? Or do we keep them out? And do we just ask the questions? Like, is that something for example, your role? Do you go, I'm gonna, I'm gonna have the meeting, I'm gonna be the one talking, and I'll pull in experts as necessary? Or do you go, I don't want to be the one talking because I want to be the one planning and I want someone else asking the questions like, how do you plan that part of it?
Ashley
Right, right, I see. So really, it comes down to, you know, rehearsal Practice, practice makes perfect. And also, so we will have a, you know, before the meeting, we'll have a rehearsal of the meeting. And typically, that involves also, you know, the smees presenting. So what would normally happen is, we would receive the responses, we would want to ask, you know, we would want to center our discussion on these three key topics or key questions that we've received response from FDA, and we would identify who is going to if we have additional data to present who's going to present that data and typically wouldn't be the SME, I feel that's, that's the best way to go, they have the clear expertise and the deep understanding of that, that subject matter. But as the regulatory expert, we would probably to tee up that, that discussion, maybe, maybe position it, you know, by by sort of establishing first what we have proposed in the in our briefing document, you know, acknowledging what FDA has given us, and maybe sitting up setting the stage for, you know, our counter proposal and, you know, our semi doctor, you know, whomever will, will provide the additional detail, and then, you know, the the discussion then ensues. And we will be there to facilitate and if we see something that we want to hone in on or particularly gain particular agreement on and understand the, the, the impact of that, particularly if, you know, on other areas or on our regulatory strategy, then it's up to us to hone in on that and, you know, interject with, with, you know, that additional question or information. And then finally, once once we reach that, it's then for the regulatory experts, who then facilitate the the agreement and alignment and ensure that that that is, that is sort of very clear to everybody what the outcome is of that, of that discussion, will be the actions moving forward, and then to facilitate on to the next, the next discussion topic. So it's facilitation and sort of, you know, leadership off the meeting, and making sure that we have all the pieces come together in the right way, and harness the best out of SMEs,
Darshan
which, which sounds like the best way to proceed. But here's the question I have, and I've been in this situation once or twice before, which is the SMEs, obviously have their pain. They're very, very smart. And the FDA comes in with a different opinion. And they're struggling with this idea of FDA. Yes, I recognize you, you have concerns, but I'm the expert in this and they they seem to Capone change into being more argumentative, sort of explain your side of that situation? How have you dealt with that in the past? Have you sort of pulled the SME and gone? Thank you so much, this is great. Or do you go this is this is an opportunity for the FDA to tell us what they want not an opportunity for us to argue? Or do you go? No, this is this is when I get to put my best foot forward and position it so that the FDA understands what where it coming from? How do you mentally approach that.
Ashley
So personally, I really try to hone in on on the key, you know, key leadership facet is communication and in the listening, and really understanding because at the end of the day, folks at FDA, no different than us, they get up in the morning, brush your teeth, take the children school, and so on and so forth. And they go to work. And their mission is to make sure that their constituents receive timely access to quality, safe and efficacious medicines. And our job in industry is to develop quality, safe and efficacious medicines for patients. So we are actually hitting on the same path. along that path, we have certain things that we need to meet and certain, you know, aspects that we have to see both for the regulator side and for industry. And so really acknowledging that understanding that and asking the right questions and really being open and kind of empathetic to to the perspective of the the regulators in the review team as to understand what they are trying to achieve and what do they need to see Because often it's it's not necessarily the the specific sort of objection, but there is something on the line that that they need to see, or they need to understand in greater detail, or perhaps they are also seeing they have the advantage, let's remember of seeing everybody's applications, we have the depth of knowledge in our products, they have the breadth of understanding across across the board. So there are things that we can learn from them, they may be seeing something with somebody else's product that then triggers a concern with ours, we don't have visibility of that. But just being open and empathetic to that and driving the conversation that's for the for the regulatory experts, and make sure we dig into that conversation as far as we possibly can to understand what's driving that objection, and how we can possibly, you know, reach a solution based, again, on scientific discussion on the guidance that FDA has put out, and also, we're making sure that we can, we can, as far as possible have a win win scenario, and there's always a way, really, I mean, you know, it used to be that regulatory was seen as the, as the policeman, you know, put the stop sign up, but really were the GPS, because there is a way to navigate, you know, through to through a product through development, you know, assuming it's going to be ultimately effective. But there's always, there's always a way to get that data, it's just really being interactive and, and partnering with FDA, to to navigate that path to delineate that path.
Darshan
So, as you can tell, we can obviously keep going forever, and we always do this, but we're well past our 1520 minute mark, where but 26 and a half minutes. So I do need to start wrapping it up. But as you know, we're gonna ask you for questions. So the first question, what would you like to ask the audience?
Ashley
So I'm interested, obviously, we have a lot of regulatory professionals listening and interested to understand their own perspective and are the one to your question, are they seeing delays? You know, and, and what are their key tips for interacting with FTA in the most productive and positive way?
Darshan
I love it. I love it. Um, my next question, what is something you've learned in the last month?
Ashley
Well, in the last month, I've learned that having a fifth child is is it is a lot of fun. But it reminds me of the the the joy of having a little a little newborn in your arm, someone who's completely dependent upon you. So I've realized that in the last month having a new baby arrived, which has been such a joy.
Darshan
First of all, congratulations, that is so awesome. It's so amazing. And I think that in a time in the times of COVID I think the best part of it is you get to have the time to actually spend the time with the baby. Which baby at a different time you wouldn't have had as much time so
Ashley
that's right and she gets she has no shortage of you know arms to hold her around this house. So
Darshan
she loves I'm so glad to hear it. I kind of know the answer this one, but I'm gonna ask you this anyways, what's something that made you happy in the last week?
Ashley
Well, yeah, looking looking at the smile on the on the on the new boys face. I'm calling it a smile, it might just be randomly picking it up.
Darshan
I think that's fair. I think we just counted as a smile. And the last question I asked you this, but I've been flashing it throughout How can people reach you?
Ashley
Indeed you can reach me at my work email address there. It is a person at Xerox comm you can reach me on the Ashley president at LinkedIn. There you go. Also via these, these podcasts, I'm sure there's a link there.
Darshan
Absolutely. You can always reach out to me, I'd be happy to connect you. And as always, actually, this was amazing. Thank you so much for coming on. We'd love to have you on again. So thank you again.
Ashley
It's a pleasure. As always, thank you.
Ashley
This is the DarshanTalks podcast, regulatory guy, irregular podcast with host Darshan Kulkarni. You can find the show on twitter at DarshanTalks or the show's website at DarshanTalks.com
