058 - "PMSR Globally" with Khaudeja Bano

058 – Khaudeja Bano

Subhi: [00:00:00] Hi everybody, and welcome to this special episode of the Combinate Podcast. We are Grace today and honored by Khadija Bono from Amgen. She's been on the show before, so I'm not going to reintroduce her because she needs no introduction. A welcome guest of, of the podcast. Welcome Kadija. Thank you.

So the, the AFTO Conference is, is coming up you're speaking. Yes. What are you gonna talk

Khaudeja: about? I'm involved in a couple sessions, actually. I'm part of the workshop. There is a pre-summit workshop that happens that takes a deeper dive in different aspects of combination product. This time for the workshop, I'm engaged in the risk management and the closed loop.

Risk management to post-market surveillance process. And then [00:01:00] during the summit, I'm moderating two or three sessions on various topics, anywhere from what to expect from an enforcement point of view for CGMP requirements, any corrections, removals, field actions. . And then more importantly the pm PMSR that I'll be hosting to still continue the evolving discussions around how is industry managing with the pm SR implementation.

And finally, there's a session that I've called, What Keeps You up At night? It should be interesting because I'm trying to get to. More of higher criticality of issues, gather those and start to gather some responses and answers on those. [00:02:00] So

Subhi: what does keep you up at night?

Khaudeja: What keeps me up at night is when I say, My thinking is always very patient-centric. It's about the patient. Am I doing, am I able to truly bring that voice of patient in everything I do? I try it, but it's often I have to think, pause and think whether I'm able to effectively do that. Hmm.

Subhi: Any, any advice there?

I mean, I know earlier in the year, you you, you, you went from safety into quality. Right. And when you're, when when you're patient safety and patient is in your title, it's obviously much easier to be very close to the patient. And, and you know, being patient centric is just part of our industry obviously, but quality is a different beast in some ways.

How do you manage that [00:03:00]

Khaudeja: To me, I haven't changed. My mindset hasn't changed. I will forever be an indiv individual who thinks about patient safety first. What the world needs to understand is in trying and making sure that we have the best quality products. . It's no different than patient centricity.

The only thing that has changed now is in the role I'm in. I'm ensuring patient safety by producing product that is the highest quality product. So it is safety, efficacy, and effectiveness to me, if you ask me. efficacy and effectiveness is my new safety.

Subhi: So having moved from patient safety to quality have, I [00:04:00] mean, I, you said your mindset hasn't changed, but your scope of work has changed. So what's that?

Khaudeja: It's been amazing, especially getting into the seat of a student where I came from. I have about 23 years of invested learning as a safety person, as someone who's done medical affairs, clinical affairs, scientific affairs, the various aspects of.

A safety like role in an r and d kind of environment. This is new. This world is new because I've had to learn and anytime you become a student, for me, I've been a lifelong student. If you look at my professional journey, There is a parallel educational journey that has happened, [00:05:00] so that that gives me a high, because I'm now able to learn and expand my knowledge.

I think there were certain blind spots that I had around what I needed to learn around quality, around compliance with a different. Not necessarily from the safety view, but why is it important to comply with certain regulatory requirements? What is the why behind that? And. It's been very enriching over the last nine months I've learned about different aspects of operations.

You know, that was a blind spot for me. I hadn't spent as much time going touring through the sites, understanding how we manufacture some of the biologics, some of the [00:06:00] drug product. I was so involved in combination product. This. Kind of gets me out of my com comfort zone and has forced me to learn.

Actually, I on one of the recent tours, I was so excited because I had in my past gone through a certification for pharmaceutical engineering. Mm. Never saw that in reality, this was bringing dusting. That knowledge and bringing it to the forefront. So it's been a very exciting journey for.

Subhi: Yeah, I always think about that because I mean, there, there are, there are things that are completely unrelated to industry that I will, I'll, I'll learn about, and then I somehow can bring a, bring a concept in, and it's always, it's, it's never this, you know, A and B, then C then d kind of translational thing.

It's always, you know, every person brings their whole breath together. Yep. I'm reading this, this [00:07:00] book called Late Bloomers that talks about kind of, you know, this. Insane idea where we want everybody to be insanely successful. You know, it's like if, if not now, then never type thing. And you know, it's usually really dotted unconnected lines that end up making a person kind of the Sort of giving them the all to say, I was recently, I was recently having a conversation with someone and I was asking them cuz early on in my career there was a, there are certain functions where they say you must do this to, you know, get to the next level.

Yes. So, like for example, you know, you mentioned manufacturing. There's this idea that you can never be a VP of manufacturing unless. Been a site manager, right? You can never be a VP of quality unless you've been a quality site lead. You can never, you can never be a VP in commercial or beyond if you haven't carried the bag and so on and so forth.

Yeah. I mean, what do you think about that? Because obviously you came from patient safety into VP of quality, [00:08:00] right? So

Khaudeja: do you think. Personally, I'm the example of someone taking on that kind of calculated risk. I have done that throughout my career where I have given people an opportunity in an area where they had no experience.

To me, what's critical is the passion. How does their passion line up with what is the key objective of the role? I mean, Someone has the capability to your point about selling. Effectively, and they haven't had that experience before, but in a different facet of the business. They've demonstrated through tough, challenging situations that they've managed to sell.

The idea it may not be a product. I think that passion, as long as you trust that [00:09:00] ability and have seen, you know them, apply some of those competencies and. , it's always worth taking on that risk. Hmm. You have to give people an opportunity somewhere. I mean I have seen people blossom in areas where, where they never had any background, so.

I'm of that thinking that people should be given an opportunity granted with the right guardrails and knowing what they bring to the table.

Subhi: Did did you do a lot of like transition planning going from safety to quality? I'm, I'm just curious because it's such an interesting switch. And I know we talked about it in the last interview.

We talked about it briefly in the last interview, but I, I recently had this conversation with someone. That's why I'm bringing it up because I'm like, Man, what

Khaudeja: a switch. So part of the ease and transition was because when I worked in the medical device and [00:10:00] diagnostic work safe peter putted into quality.

Oh, so while I have not been a quality individual, like I have reported into quality, I also think I've lived some very challenging times from a regulatory compliance point of view in my past. So if you have lived through a consent decree or a corporate integrity agreement, You by default are effectively trained in quality of the highest standard, and I've gone through both those, so that helped me be, I think, a much better prepared candidate versus.

People who have lived in quality for, let's say 20 years and not seen any of those tough times and come out of those challenging situations. So I think [00:11:00] that way I was lucky for indirectly having gone through those times.

Subhi: Yeah. You, you came out of it alive, essentially. And Exactly. I completely agree. I mean, I've, I've seen, I've seen situations before and, you know, seeing an organization transform every, it's like the little queue versus big queue, big queue distinction, right?

So everybody, everybody becomes like a shadow. Big queue if you go through like an issue like that.

Khaudeja: Exactly.

Subhi: So I wanted to before we jump into that, you, you were talking about risk management and you know, the workshop that you're, you're gonna lead. And so the importance there, but in, in pharma versus med device, right?

There's the QRM ICH versus 14,971. And, and they're in some ways similar, but in some ways kind of different. And there's you know, TIR 1 0 5 and, and that where tries to reconcile, but. Can you talk a little bit more about that?

Khaudeja: Yeah, so I think again, if you step back and think [00:12:00] about what's expected under each of these regulations and standards and requirements, ultimately the expectation is to have the right level of controls.

Firstly, the. Knowledge about what's critical to your product, critical to the best quality, What's the essential performance requirements in terms of your combination product, and then do you have the right risk attribution to those? Plus, do you have the right controls in place in addition, How effective are your controls?

How much of the rest of your risk are you willing to and able to carry? Passing that red face test of, have you done everything to reduce your risk to as. [00:13:00] Low as reasonably possible, and I throw in the word reasonably possible because it's still a practical world, and you need to make sure that when you are doing certain trade offs, you are thinking through the impact that has.

Either you pay the price up upfront or you pay it after the fact. So, The smart, intelligent organizations will decide and pay the price up front. Do a good job with risk management, make sure it's a closed feedback loop. Your post market is continuously, proactively feeding your design, your label, different aspects of your product, even after it has gone to market and you keep.

Least burdensome to update [00:14:00] and maintain it and make sure you are continuously evolving your product as you go through this exercise.

Subhi: Understood. So you're talking about the, the linkage to lcm essentially? Yes. Yes. Okay. Dialing you back to sort of the conversation that we were having as, as before we started recording.

You know, different companies call things differently. I've, I've been personally looking into trying to understand the promotional versus non promotional compliance and understanding who can say what when, and, and that I just find that area really interesting. And learned recently about sort of the history of the medical affairs function.

Yeah. And. Companies have medical affairs, they have pharmaco vigilance, they have patient safety, and sometimes different variations. Patient safety, they have clinical and medical groups, and sometimes the folks that are working pre-development are different than the ones woken po working post-market.

Right. And, [00:15:00] and then you have country specific if, when you have like you know, the, the local offices in some cases. And so I'm just wondering since you've worked and, and add to the mixed drug versus device, right? Yes. You know, as if it wasn't already convoluted enough. Can you just explain at a high level the difference in responsibility for some of the groups?

Khaudeja: Sure. I'll take a stab at it, but I want to throw in the, that every company has, its set up very differently. For sure. I'll start with devices because I think that's very clear and crisp in the device world. And the diagnostic word, and this is based on my experience with the organizations have been at, or in talking to peers that I network with in the device word, When you use the term medical [00:16:00] affairs, Medical affairs includes safety assessment, includes compliance, and to a certain extent, includes customer interactions when it comes to quality related issues.

So, and usually that role sits in quality. Those physicians understand the reporting requirements, the life cycle management requirements for devices. They play a role in safety aspects. Of the entire life cycle management, including, as I mentioned, quality issues. So for example, if you are a medical affairs individual in devices and [00:17:00] diagnostics, you are responsible for contributing to the user needs, the product, product requirements, review and approval.

Pre-market documents, the safety sections of those. You are responsible for reviewing and approving the safety aspects of clinical trial protocols, investigative brochures you're responsible for on market seriousness assessment, serious injury or non-serious. Malfunction Reportability assessment, health hazard evaluations, medical opinions, meeting with customers should they have quality issues and need to discuss safety aspects of [00:18:00] things, field actions, field corrections, and removals.

And any audits and inspections related to all these topics. Mm.

Subhi: So that's, that's all it, It's so crazy that you just boom, boom, boom, boom, boom. It's like, you're it, You said it almost like you're reading out for prompter and I know you're not. So that's,

Khaudeja: I actually lived it. That's why that's been predominantly my

Subhi: life.

That's really cool. So one of the things that you said is medical opinions to what?

Khaudeja: So let's. There is an individual complaint and they got investigated it and let's say it's a particulate in a prefill syringe or in a while. Oh, I'm talking devices. So let's say you get a complaint where there is a particular that was clinging [00:19:00] onto your syringe.

It's on the outside. It was in the package, but it's secondary packaging. As part of the complaint investigation, you may have a process where you have discarded the unit you go through, look at your internal lot and confirm that it was a. You know, one off issue. It is a good idea to get medical opinion on, you know, What do you think is the impact of that kind of an issue that should it come in contact with a patient, what would happen?

And again, the medical affairs person has to look at. Where was that particulate? Did the secondary packaging go through? Sterilization is so those kind of assessments are rendered in a medical opinion. Understood.

Subhi: Okay. So, [00:20:00] so that's, that's medical affairs essentially, from what I understand from what you, That's medical affairs in device.

They're pre post market. They're doing safety assessments. They're doing compliance, whether it's, you know, including audits for everything related. They're doing the DHF work, making sure that the user needs and design constraints, design inputs, all that are well defined. They're working on the safety elements of the risk documentation, like aj.

And then they're doing any type of on market serious injury or suspected malfunction. Yes. Hhs. Okay. Understood. So that's, that's device medical affairs.

Khaudeja: There are other functions. That's it. Within medical affairs that are also physicians that have very different jobs, so there are is a group that's led by a group of medical science liaisons.

These are also physicians that sit in medical affairs. In the device and diagnostic [00:21:00] world, they can choose to organize it differently within different organizations. But this is a group of physicians that can discuss research from, from a peer to peer, physician to physician point of view. They are given the right training and are.

Provided tools and mechanisms to have those scientific discussions participate in interacting with key opinion leaders, gathering information. Granted, there's a very fine line and they are never to promote off-label use. You were talking about the promotional aspect. None of the functions within an organization.

Should or will ever try to suggest off-label use or promote it off-label. If let's [00:22:00] say a physician or a healthcare professional is trying to practice medicine differently where they are using a product in a different way and want to understand, let's say the scientific background, the construct of things Certain, you know, technical details.

This team of medical science liaisons can have that discussion. With, that they can share in the scientific peer to peer manner what they know based on literature and things that are published.

Subhi: Yeah. I, the, the, like I said, this, this area is pretty interesting to me. I, I had an attorney on for a couple episodes and we talked about, you know, the promotional, what, what the commercial folks can do, and then the non-promotional, what the, what the doctors can and do.

Yes. And I find it to be really interesting and. A lot of it is grounded in free speech. And, [00:23:00] and yes, you know, it, it's really

Khaudeja: cool. There's another group that's the clinical group that group of physicians are responsible for conducting the clinical studies and managing the clinical studies. So they are, they sit in clinical affairs, which is often reporting into r and.

And they are directly involved with the day to day operations of the clinical trial. Safeguarding, you know, the rights of the subjects involved in the clinical studies, but also with the clinical operations the ensuring that the conduct of the. is really happening in the best interest of the patients and subjects,

Subhi: and so this isn't like primary investigator.

Khaudeja: They are the primary. Oh, they are. [00:24:00] So it depends. If you are conducting the trial as a company, then these will be your primary investigators. Often you partner with universities, with hospitals and the primary investigators sit in those institutions, and these are peers within the organization that provide the oversight and make sure.

They are there to represent the sponsor, which is, which will be the company and partner appropriately with the PIs.

Subhi: Understood. So that's, that's clear essentially. If, if, if you're doing the study, then they would be the pi if they're coordinating the study with, with the partner, then they would oversee the pi, right?

Yes. So that's clear. Any, anything else in, in device or is it medical affairs? Medical science, liaison and clinical.

Khaudeja: There is a scientific affairs usually that sits, [00:25:00] also sits in medical affairs or in the same group reports into the same group, but they are more the technical experts on the device. The instrument depends on what kind of device you are talking about.

And they partner very closely with the engineers. So if they're, they, they also work on the entire product life cycle, but they are more involved on the technical and scientific aspects of things. Okay. So

Subhi: I've, I've worked with, with some of those folks before, I guess I didn't know that they were called Scientific Affairs, but, you know, nurses and doctors that were deeply in, in involved in the design and it's like, is this really what we would see in clinical use?

Yeah. You know, that, that type of thing where they're like the user would never do that, or, you know, that type of thing. Yeah. So that's really interesting. Okay, so pharma.

Khaudeja: In [00:26:00] the device. Word. One final thought. Oh, sorry. In the device word there, depending on class of device, often in class two, class three devices, there are physicians, technologists.

That are a part, if not a part of majority of the commercial organization because most of the high risk devices. The commercial team member is present when the device is implanted or deployed. And in order to do that effectively, you need to have the right qualification. I have seen, for example, in the pacemaker world you, I've seen some highly [00:27:00] qualified.

Cardiologist in the commercial organization working with the physician who's actually doing the implant. Mm. The same goes for stands and you know, orthopedic products. You need to have that kind of expertise in your commercial organization. Yeah, makes sense. Those are usually MDs with mba.

Subhi: Got it. Is there a, a big difference between how it's set up between device and pharma?

Khaudeja: I would say yes. Okay. Pharma, you see mostly, I mean, just talking about this function, pharma, you see pharmacists doing a lot of the marketing and. I have seen physicians in the pharma world that come with that therapeutic area expertise, but pharma, it's very different than [00:28:00] devices.

You also have to understand the life cycle of a device is much more condensed. The turnaround time, the study durations, everything is very condensed for a professional. You could in your lifetime, see, depending on what class of devices, 10 to 20 devices go from start to finish. In the pharma world, if you get to see two to.

It's huge because of how large the funnel is, how many successfully make it to the finish line. You could work in a multitude of products, but that is the significant variability in, you know, from one industry to another.

Subhi: Understood. And then in terms of like the I understood what you said about the the folks that are in the commercial org maybe coming from different.

Competency areas. But what about the medical affairs, [00:29:00] science liaisons, clinical? Are they typically the

Khaudeja: same or No, Very different. So pharma likes to do everything big. Everything spread out. And that's why I was setting the stage with the timelines. So if you have the kind of magnitude of. A study, you know, you have studies going on for seven years in pharma.

So in pharma, the setup is, there are groups that sit in clinical affairs that do very similar work like I described in the device world. But that's a very well structured. Large organization of physicians, safety physicians doing clinical studies or supporting clinical studies. Then you have [00:30:00] a group of physicians sitting in pharmaco vigilance and patient safety that are oftentimes, Directly reporting into the ceo.

Their leadership directly reports into CEO or as part of r and d, and their job is more broken down into, if I can say three areas. So one is pure safety operations, where they are processing all the adverse events that are coming. And they are responsible for decision making, application of regulatory requirements, whether something needs to be reported or not.

After. So that's the group of safety operations. Then there is this therapeutic area safety group, which in many organizations, at least mid to big [00:31:00] pharma is organized by therapy area. You have a leader in that therapy area, and then you will have global safety officers. So there will be a therapeutic area head who has expertise in that disease state.

The most common you'll see is immunology or cardiology or cardiometabolic women's health. Renal health, mental health, and then you have global safety officers who are junior physicians who do the day to day operational safety review and ensuring that the product is safe. They monitor, Do.

Active surveillance. Hmm. There is a different group that does, It's mostly, I would say, nurses in that group that does aggregate safety reporting, which is also, there is an operational aspect to it, and then there is the strategic aspect to it. So this is a huge [00:32:00] organization. Purely based on volumes of adverse events that ha come across are constantly spending time making sure their product is safe, and more importantly, ensuring the benefit risk profile is maintained.

And if the label needs update, if managing signals, monitoring signals, that's what they do. This team is also involved in. From a pharma perspective, dear healthcare communications, so if similar to let's say field corrections or communication field actions, this team is involved in those communications.

Certain pharmaco vigilance group will. The same team handle the entire product lifecycle, so it'll be the same safety group supporting the clinical [00:33:00] studies safety versus the on market safety. In certain organizations, there is a wall between, that's the clinical group, it has a meta image of the therapy areas, and then the arm market group.

Then there is. I touched on medical affairs. Medical affairs in pharma. Works very closely with the commercial team, and they are the go-to team for supporting. Commercial organization during various like conferences. Having that scientific dialogue engaging with key opinion leaders, getting industry insights.

So there is that group. You talked about local safety teams, many geographies, many organizations and various geographies have local [00:34:00] safety officers that partner with interestingly local quality representatives. And it is usually to. The diverging regulatory requirements for safety and quality in those geographies.

But there's a lot more They do. They are the contact with the local, say local bodies, regulators, notified bodies. So that, I hope I caught all the different functions you had talked about. So

Subhi: there's, there's clinical affairs. There's, there's safety physicians that are working on the clinical studies.

There's pharmaco, vigilance and patient safety. You said they typically report into the CEO or r and d. Within that, there's three arms. Usually each company is set up different. One of 'em is purely safety operations, and they're [00:35:00] managing the flow of adverse events that are coming in. A parallel function to that is a set of the therapeutic area leads whose responsibility is not on managing adverse events.

They're responsible for being deeply knowledgeable in a certain therapeutic area, and when there's adverse events that are not cut and dry, perhaps they get involved. And you said there, you know, there's, there may be perhaps hierarchical because the level of knowledge there is really important where there's a global safety officer for a therapeutic area and then from there flows more junior folks who are also experts in the area.

But there's a chain of command there that's important and it makes sense. And then you said there's a aggregate safety reporting function that is typically primarily. Maybe non physicians, but still HCPs Who are responsible for some of the field communications and some of the active surveillance.

Yes. As well as ensuring that the [00:36:00] benefit risk is continually positive, right? Yes. Additionally, there's medical affairs who is, is kind of similar to what we talked about in the device side, but. You know, essentially it sounds like they're the guard rails for the commercial folks, right? Yes. From a scientific point of view.

Yes. And then the last part is the local safety. And we talked about some of the local requirements, which is a really good segue into what I wanted to talk to you about and we're short on time a little bit, but that is some of the compliance requirements around reporting for combination products O us.

Yes. If you could, can you, can you speak to it broadly? We don't have to go into like timelines and stuff like that, but maybe the different appetites or the, the different permutations of reporting cuz we have the malfunction and serious injury in the us The five and 30 day report and that, that's, it's funny cuz I, I, I I started off, before we started recording, I was saying that my perception is that because part, you know, [00:37:00] part four Part four, Part B came out later that it's less mature.

But you said because it was a more controlled launch. It's actually more mature but less known. And so all to say, right in the us there's some. Some adoption and clarity, but os I feel like it's maybe less so. And so if you could

Khaudeja: talk about that. Yes. So according to what I'm observing, there are three, and this is Mo.

More my opinion, There are three models that are emerging in the post market safety space. Four combination product. One, you are highlighted, the US model where there is an effort to reduce redundant reporting where possible. Then if you look at the eastern part of the globe, There are specific requirements in certain geographies [00:38:00] for redundant reporting where it's not clear to the device arm and the drug arm of those particular regulatory agencies.

Then Europe sits in the middle, which is almost a hybrid for single Integral. The requirement is for us to treat it like a drug or device, whatever the primary mode of action, but for co-pack or reference material, reference product, it's following. If I can say more of the Uslike approach. In certain cases, , but the variability is so significant.

Depending upon the risk. You have anywhere from 24 hour requirements in, let's say China per certain risk to public health [00:39:00] all the way to a 45 day B P D R requirement for a biologic in the. And what makes it even more challenging from a company or an in industry to implement is there's variability between calendar days versus business days.

There is variability from a point of awareness. How do you define day zero? It varies. What is my day one? It varies by geography, so, It is challenging. I mean, there is a strong desire to have some level of harmonization, even if we can come up with alignment on. The reportability timelines for serious injuries, serious risk of harm to the public and malfunctions that have [00:40:00] the potential to cause harm.

I think that would be a big win. Today we have. 24 hours. Then there are certain geographies that have 48 hour reporting requirements. Then you have five day reporting requirements. You have 15 days, 30 days, and 45 days. I don't know if anyone has seven days, but that is the divergence you are seeing. And as you can imagine, when we are using global databases, many of the big players in that space have different implementations for the different geographies.

So that does make life easy. But for the midsize to small c. They have to manually ensure they are compliant, and that's where you [00:41:00] see the decentralized model, where you have the right safety and quality people sitting in the local geography to effectively meet the needs while. The essence is the same. I think the format significantly varies between all these geographies.

If you just look at Asia Pack area, there isn't alignment on even one topic in combination product across all the countries. So that makes it very difficult, even if you have a regional office taking care of things, because then you need to have someone who understands that local specific require.

Subhi: Got it.

And so that, that last point makes sense that you know, my follow up was gonna be, I mean, is there ongoing work to harmonize? But if there's [00:42:00] no agreement on what a combination product is, what do you harmonize against? Right. Is that the right answer? ?

Khaudeja: Yes. I think to your point earlier about maturity, I think as we evolve as.

A word and get more globalized, more globally aligned, we will come together and harmonize. I don't see that happening in the next two to three years. I think what will force us to do that is introduction of digital solutions to make this even more complex. We are starting to see that when you have digital solutions or digital products embedded, that's muddying the water so much that there is a need for us to step back and look at what is our definition of our product.

And we, we will get there, but [00:43:00] it's going to be a painful process in the. And

Subhi: so that's where things like Emed may help pave the weight, you're saying? Yes.

Khaudeja: Yes. But again, that's a very narrow scope. It's a small representative of the diversity of requirements. I mean, latest, I think PMs heart requirements came out of Malaysia.

So you have Malaysia, Saudi Arabia, that have pretty mature. Requirements. Now they take, I'm almost positioning it as they are taking the best of what they are seeing and bringing it together. Well, very

Subhi: good. We're, we're really close to time. Last last question for you. What is something you're excited about?

Khaudeja: I'm really excited about. How much collaboration is happening in industry and how open FDA [00:44:00] has been in dialogue, discussion to understand industry's pain points and work with us to provide the clarity. Very excited about it.

Subhi: Well, excellent. Thank you so much for coming on again, Khadija. The honor is all mine.

Khaudeja: Thank you. Pleasure to be here.