Transcript
Speaker: Welcome to Clinical Data Talks, a podcast brought to you by CRS-Cube. I'm your host, Sylvain Bertelot. Join me and industry experts as we discuss the latest trends impacting the world of clinical data.
Speaker: Today, I'm thrilled to welcome Kodeja Bano to the show. With over 20 years leadership across some of the top pharmaceutical companies, Kodeja brings deep expertise in diagnostics, therapeutics and combination products.
Speaker: She's been a key voice in shaping the regulatory landscape, notably serving on the working group that helped establish 21 CFR Part 4 regulations.
Speaker: Speaking today from her own personal industry experience and expertise, she joins us to discuss compliance and safety management for combination products, a topic that is becoming increasingly critical as drug device innovation rapidly accelerates.
Speaker: Hi, Khodeja, and welcome to the show. Hello. Good morning. ah So we had a very fascinating discussion actually you when we prepared for this podcast. So I can't wait to hear all your ah your experience in combination products. And it's something that I find very interesting is that you told me that ah with something like GLP-1 auto-injectors, the healthcare care is now moving in the patient's hands. So based on that example, why, ah from your point of view, is it critical for our industry to understand the nuances of of safety for combination products?
Speaker: Thank you. Thanks for that question. First and foremost, I think some of this acceleration happened more during COVID.
Speaker: So COVID inadvertently, while it brought a lot of challenges to us, this was the silver lining of sorts where it forced all of healthcare and specifically our industry, pharma industry, to think about how can we facilitate bringing some of these products in the hands of our patients in the convenience of their homes.
Speaker: Prior to this, there always has been insulins, use of insulin in diabetics that had some flavor of use in the hands of patients. But now with GLP-1s, I think it has just the sheer volume.
Speaker: The magnitude of shift has forced us to think differently. And I think one of the biggest changes we have had to think about is the environment and the ecosystem surrounding the use of these products.
Speaker: Therapies that used to sit and be administered by HCPs now need to be usable bye you know, common people.
Speaker: People who, um regardless of age, you know, some of our elders are now expected to use some of the the products. So it's interesting that now from a usability, from a human factors point of view, we need to really think about the different lighting in people's homes, the different environment in which they are sitting while they are using these products.
Speaker: So It has forced us to make our products much simpler to use, easy to use, more um clear instructions for use, but also think about making them as safe as we can with, for example, needle safety guards, needle protection.
Speaker: So I think it has not only helped the patients, the healthcare professionals, but also us as an industry to expand the thinking.
Speaker: Yeah, so what you're saying is that you're you're moving the end user. And it's true that we don't necessarily think about it because we we see the evolution of drug devices as a positive, but there are there are a lot of risks associated to it when you move from clinicians doing the procedure to a patient doing the procedure.
Speaker: And I imagine they also need to think about what if it it gets in the wrong hands by mistake. So I like that. We jumped right into it actually. But I think it might be interesting to hear what your definition of combination products is nowadays. and how you think the evolution we've seen in recent years has shifted the line between a traditional pharma and medtech?
Speaker: um There are very clear regulatory definitions, at least in in some of the key regulatory um environments. So from a US FDA perspective,
Speaker: If a drug, a device, and biologic, either two or three of them are combined together, that's defined as a combination product.
Speaker: A very similar um but slightly different definition from Europe perspective Japan has its own regulatory definition. and So I've oversimplified it to say any combination of a drug and a device um is probably how we should think of as a combination product.
Speaker: I think at this point, there are more than 11 countries or jurisdictions that have some flavor of a definition of combination product. even though it varies slightly, yet the concepts are the same.
Speaker: And oftentimes the way we are seeing it show up is either um in the pharma world as drug delivery systems or in the device world as devices that have a drug component to it. So prime example that comes to mind is a drug eluding stent.
Speaker: so the stent has always been de deemed a device but once you put a therapeutic chemical entity on top of that then it becomes a combination product where the key aspect we need to focus on is what is considered the primary mode of action so in the case of the drug eluding stent because it's a metallic scaffolding it's a mechanical device as the primary mode of action versus in the drug delivery system.
Speaker: The drug usually is what is getting the therapeutic benefit. So that's the primary mode of action. So that in a nutshell is what combination product is. I want to say us has the most advanced clear definition of three types of combination products.
Speaker: Single integral, where the drug and device are a single entity. The second is co-packaged, where you co-package a device and a drug together.
Speaker: So it's ease of use oftentimes. And then the third one is cross labeled where two different manufacturers have the two different entities, but in their label, they reference the other product.
Speaker: And in order to achieve the therapeutic or the diagnostic objective, both have to come together.
Speaker: You've described a lot of nuances which people may not necessarily be aware of or really appreciate what the impact can be on regulatory requirements, safety data that you need to collect.
Speaker: So what's the importance for a pharmaceutical company or a medtech company to collect the data of that combination, essentially?
Speaker: Very fair point, because if you step back and think of the evolution of pharma as an industry, it is it has been there for much longer.
Speaker: than the device as an industry, right? so So therapeutics in some sort, even if you go into the olden ages of some herbal or natural therapies, right? So pharma and its side effects and use of pharma to treat has been a very well-established science in my opinion.
Speaker: When you look at some of these products that we now call combination product, some of them have been on the market for longer than 20 years and they would never call combination product.
Speaker: They were considered simple or therapeutics. And instead of a while, they were put, they were considered secondary packaging or, you know, tertiary packaging.
Speaker: or container closure even in some instances. From that to now requiring very structured regulatory thoughtfulness that needs to be put in place to assess, even before assess, develop, design, develop, evaluate the interaction between that device constituent part and the drug.
Speaker: to understand that together they are achieving what we need to deliver for the patient's benefit, it is in itself a whole new science that has evolved, especially over the last, I would say, 15 years.
Speaker: Once you are in this realm, it also very clear that based on your primary mode of action, As a pharma manufacturer, it is the obligation of a pharma company to own the safety, efficacy, effectiveness of the product as a whole.
Speaker: And you can imagine from monitoring, for example, side effects and safety related topics for the drug product or the biologic or the molecule to now having to make sure that, for example, there isn't accidental needle stick injury.
Speaker: There isn't um glass breakage. Those is while they were gathered in the past as part of some of the safety data, it now needs to be looked at very differently and to be leveraged in specifically risk management of the product.
Speaker: the device constituent part, also to close the feedback loop and use some of this information throughout the product's life cycle, including clinical, to feed it back into the design development of the next generation device, next generation product.
Speaker: And I think though there are certain gaps that exist right now in that thought process. Oftentimes because the device constituent parts are not necessarily manufactured by pharma, but sourced from somewhere else.
Speaker: Yes, and it's this chain that is, imagine, very difficult to manage. And i mean, obviously, we're in a world of risk management, but traditional medicine compared to med device have in the past been very different in terms of risk management, safety reporting.
Speaker: So you shared what the regulators expect. How does a sponsor then turn that into the right kind of data for the regulators?
Speaker: um I think there are so quite a few examples of organizations that have nailed it. I think especially during clinical trials,
Speaker: where you are using these drug delivery systems or combination product, that is an excellent opportunity to start asking the right questions about the device safety, device efficacy, even feedback.
Speaker: I think I've seen companies that have really done a good job of asking very targeted questions to make sure they leverage that data to build a robust label instruction for use.
Speaker: And while you are um in a clinical setting, it's almost pristine environment, right? Where you have the um oversight, the rigor, the significant compliance, attention to detail,
Speaker: I think it's an opportunity where you really can hear the voice of your patients and your HCPs as they use these products. Because some products are simple, but some are very complex.
Speaker: And the more we can gather that information with the right context, I think that helps you inform your label,
Speaker: but also be better prepared for post-market surveillance. So when you launch your product, you have a deeper understanding of where people can tend to use it differently.
Speaker: Because in the clinical studies, you've gone global many times, you've seen different um you know human factor related to things play out.
Speaker: in common use. So I think that's an excellent opportunity for pharma as an industry to start building robustness and gathering information.
Speaker: Post-market surveillance obviously is the by default, the go-to place to get this kind of information. There is also an opportunity to have targeted questionnaires, feedback, especially on things that are critical to use of your product.
Speaker: Coming up with specific follow up questions when you get complaints, I think that's a great opportunity. But also when we have our commercial marketing colleagues out in the field, they hear some positive feedback too.
Speaker: And we don't necessarily have a robust process as pharma companies to gather that positive feedback too.
Speaker: We need to build that in order to do a good job of the benefit risk, we need to do that proactively.
Speaker: Yeah, it's fascinating. You don't need patient feedback necessarily. I mean, it's always good to listen to your patients, obviously, but that's not an actual need from therapeutic point of view. But when they use something that's very important, you made a very good point here.
Speaker: And I imagine that it's actually very difficult to manage that because Like you said, in the clinical trial setting, you know your patients and you can build that feedback loop. It's much more difficult to do that once you're in market and your product is used by thousands of people. You don't know who they are.
Speaker: You're not meant to know who they are. ah So yeah, I love that. I love that. um I want to go back to something you mentioned earlier, because you you said that regulations now are meant to capture what is specific to combination products. but I think you alluded to the fact that it might differ per country. Are there big differences
Speaker: I would say some of the big differences that exist right now is how you report um post-market data, safety data.
Speaker: So, for example, in the U.S., you are expected to report only one single report to whatever has been your primary mode of action related regulatory body.
Speaker: So if it is a drug primary mode of action, then CEDAR, you would submit a single post-market safety report, but you, there are provisions to include both the drug information and the device related information.
Speaker: um Very similar with a Europe. In Japan, you would expect it depending upon the issue, sometimes submit duplicate reports, device related reports to the device agency um and drug related reports to the drug agency.
Speaker: So those are some nuances. One other thing that I, especially from a European perspective, EMA is you need for combination product, notified body opinion, which is an additional step now.
Speaker: for combination product um on the device aspect or you need the device to be CE marked. So that adds a little more burden on the pharma organizations to better understand and almost build that in their timeline for a product lifecycle, for a product launch. So those are some high level nuances that come to mind. The regulatory pathways um have their unique nuances, how you submit, what data you include.
Speaker: um So it's it's interesting. um Also, I think from the post, ah like once you launch post launch, Audits and inspections are slightly different.
Speaker: What I really appreciate, one of the latest evolutions that's been, um I would call the first step in the right direction of harmonizing across geographies is FDA coming out with QMSR requirements and shifting from QSR to QMSR. which actually acknowledges ISO 13485 as a standard, which is globally acknowledged. So I think we need more and more of those kind of harmonization efforts, where as things come together, it makes it consistent for companies that are global to have that robustness built in, without having to think about the multiple nuances and iterations for the various geographies.
Speaker: Ultimately, I think every regulatory body and authority has the same goal of ensuring safety, ensuring efficacy, ensuring compliance. It's just how their respective regulations have evolved over a period of time that bring in those nuances.
Speaker: and It's very important to understand those nuances, obviously. i mean, it goes without saying that you need to know your regulations in our industry. But when you move from maybe traditional medicine to combination products, you can't do that necessarily easily. You need to understand what you're doing.
Speaker: ah i want to I'm interested in your experience in that working group you were involved in 21 CFR Part regulation.
Speaker: Are there any learnings, for example, that you gained from that experience that that you think could be beneficial to apply to our industry in general?
Speaker: Absolutely. i think that was the first time in my experience, at least for 20 plus years, I've now been in industry for almost 25 years, where industry joined hands and really partnered with the regulatory body from a US FDA point of view to have an open discussion and dialogue. And I have to say thanks to the Office of Combination Product that um was willing to hear the industry perspective, hear what
Speaker: what we had to share, but also spend time to understand what was their objective as the regulators. So we could also align as an industry.
Speaker: And I think that dialogue highlighted the fact that, again, as much as the regulators have that goal as companies, we would love to have the most safe and most effective robust product out on the market.
Speaker: Once we align that it's a common goal that we are aspiring to achieve, it becomes very easy to then think of how can we set up the environment within the industry and with the regulators to ensure the best state of compliance.
Speaker: And I think ah one of the key things i tried to do differently in this case was because there is a huge technology component to this post-market safety reporting. So it was for 21 CFR Part 4B specifically.
Speaker: I also brought with us as an industry representative body technology companies at least the major three or four players who ah have this system that most of our companies use to report safety reports to the agency to make sure, i mean, yes, it's the people, it's the process, but technology oftentimes gets forgotten and missed.
Speaker: So to me, that was an aha moment that having all three at the table discussing with the regulators to make sure we set up the most robust solution to meet all our needs was a profound outcome.
Speaker: And I can say those activities happen very actively, especially in Europe, there is, you know, device representative bodies that industry has. um I'm seeing more and more of that collaboration now.
Speaker: My one recommendation would be, please consider including the technology partners. It makes a huge difference when all three of us are heading in the same direction with the same timelines in mind.
Speaker: Yeah, and I bet that it makes it faster as well to implement eventually because you've you've addressed all the questions upfront rather than releasing something and then interpretation may vary. It's not as simple as it was expected to to then put that into into the the workflow. so Yeah, um I love hearing about those cross industry collaborations because that that makes me feel like we're all going in the same direction which we should be doing.
Speaker: Well, I feel like we've only scratched the surface, but unfortunately we don't have ah too much time on our hands. But I have one last question for you. um What's the best piece of advice that you've received in your career that you consistently apply at work?
Speaker: To me, the best piece of advice I have received was always look at a problem as an opportunity.
Speaker: And you don't achieve things till you put yourself out there in the riskiest of situations.
Speaker: And when I think of my entire career
Speaker: I have raised my hand for projects, initiatives where it seemed almost impossible to achieve things. And um it hasn't been easy because when you're doing it for the first time, you are navigating an area for the first time.
Speaker: it is challenging because you are navigating totally unchartered territories. But every time you look at a problem and think of, if I can solve this, I would have made one step forward in growing.
Speaker: Because it always comes with humbling experiences. It highlights how much you do not know versus how much you know. And that has been the foundation of my personal and professional growth.
Speaker: That's wonderful. I love that. And you're right. If you don't challenge yourself, you don't grow. Yeah. yeah Amazing. It's been so nice talking to you, Kodeja. Thank you so much for taking the time. I'm sure people will ah listen to this and and learn or understand more about combination products. So yeah, thank you very much. It's been a pleasure. thank you. Thanks for the opportunity. I really appreciate it. I want more and more people to be curious.
Speaker: Me too. That's why I'm doing this. And thank you everyone for watching or listening to us. You can find more clinical data talks episodes on the CRSQ website.
