Effective Supplier Management In Drug Delivery Development With Suttons Creek

In this episode of In Combination, Albana Thorpe and Max Lerman from the technical director team at drug delivery product development consultancy Suttons Creek discuss with host Tom von Gunden, chief editor at Drug Delivery Leader, considerations around supplier relationships in product development for combination products and other delivery devices. Albana and Max share perspectives on quality management, documentation, usability testing, regulatory pathways, post-market design changes, and other aspects of supplier controls. 

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of In Combination. My name is Tom von Gunden, Chief Editor at Drug Delivery Leader, and your host for the series. For today's In Combination, I am joined by two folks from the technical leadership team at combination product and drug delivery consultancy Suttons Creek. And for that conversation, I want to welcome Albana Thorpe, who is a Technical Director there.

Welcome, Albana.

Albana Thorpe, Technical Director, Suttons Creek:

Thank you, Tom. Good to be here.

And I also want to welcome Max Lerman, Associate Technical Director at Suttons Creek.

Max Lerman, Associate Technical Director, Suttons Creek:

Thanks, Tom.

Well, it's my privilege to have you here. Let's just go ahead and dive in. So, today's conversation is going to be around the topic of supplier management, supplier relationships, and, ultimately, supplier controls and regulatory expectations and guidances around that.

Let's start at a fairly high level: When you think about supplier relationships, supplier management, even before we get into the specifics of how it applies to drug delivery, for example, what are some of the key considerations that come to mind and that you think folks should have front-of-mind in biopharma organizations as they look to evaluate, select, and build a working relationship with suppliers to the industry?

Thorpe: I can start off and then hand it to Max.

So, one of the key things I think of when trying to select vendors or suppliers is ensuring you're assessing their maturity as an organization, specifically around [their] quality management system. We need to ensure we're assessing the robustness of their QMS. We're taking a look at the history of regulatory inspections. Do they have a good track record of compliance? Because as we all know, a weak QMS leads to significant, either regulatory or launch risks. At the end of the day, the goal is to launch your product.

In alignment with that, ensuring that you've got strategic alignment with your supplier. So, ensure that the supplier has the capability to support you, and has a long-term strategy plan to support you. You don't want to select a supplier that can only get you through development, but you want to hit that commercialization goal and that launch goal and that ramp-up.

And if you don't align that early on, downstream when you actually need to launch or need to ramp up, that's when conflicts typically occur.

So, those are just a couple of my thoughts. But, Max, I'll hand it to you as well.

Lerman: Yes, I would try to approach these with, I don't want to choose my next supplier, but be my next partner, right? You want to have longstanding and really fruitful engagements.

So, the example Albana brought up, your quality management system: Are they [suppliers] able to handle things on your behalf? Are you comfortable with them handling things on your behalf and outsourcing those things to you, right? One, to make your things more efficient. But wouldn't you rather the expert in that space be investigating and addressing issues firsthand rather than having to pull the strings from afar, literally or metaphorically?

And there are a lot of ways to dive into that with individual suppliers. But we all get our first impressions, and there's something to be said about them. Is this something that you're willing to work with in the long haul? And if the answer is no, then thinking critically: Is that a conversation — a relationship — you're willing to continue to invest in?

Yeah, I didn't really prep you for this — and I hope it doesn't put you on the spot; I don't think it will: But, in listening to your comments about things to look for and watch out for, I'm wondering if you can give any examples or advice around what could be a concerning thing that seems to be missing that you might want to look at again to see if it's there and you just didn't see it the first time?

Lerman: For me, when I've had conversations, either on behalf of or with clients, it's been, well, what are you willing to share? People should be proud of their work. You can take out names, you can anonymize information, but if they're not willing to share information under an NDA, that should be a huge red flag that maybe this is not someone who is willing to be a partner with us in the long haul.

Gotcha. Albana, anything you want to add to that thought?

Thorpe: I agree. That was actually what was in my mind. And what’s specifically written in a quality agreement with your supplier is, what are they willing to share? Are they willing to support you if you get an information request from the agency? Are they willing to provide you with the documentation you need when you're ready to file?

We've seen both sides of the coin where there's companies that are very transparent and are willing to give you summaries, and then there's companies that just, it's a complete block and it's like pulling teeth a little bit. So, that's definitely something I agree with Max to look at in the very beginning. And typically that's cemented in an agreement, and if they're not able to cement it in a quality agreement, then that's a red flag.

Gotcha, gotcha. Well, thanks for the take at the highest level of thinking about supplier relationships.

So, let's now take it down to the level, specifically, of folks who are working on product development around drug delivery or combination products or whatever it might be at the ground level in terms of product development. What additional, specific considerations come into play around materials or component parts or devices or services when we're talking specifically about delivery?

Thorpe: So, when you're working in a development program and you're selecting a supplier and they're providing you materials, sometimes it tends to be a transactional mindset where I'm buying X amount of parts from you and then that's it. But when you're developing a combination product, it needs to be co-developed, right? You have to have a partnership with your supplier because you're going to need information from each other in order to be successful at the end of the day. You're going to be sharing specifications, you're going to be sharing documentation and data, test data that you're releasing these parts to.

So, I think ensuring it's not just a transactional relationship, but it's a co-development is key. That'll also bleed into when you're performing risk management throughout your whole development cycle, as you're building out your FMEAs or your risk control strategies. Those need to be in concert with your suppliers. You can't do that in a vacuum. So, that leads to what Max said earlier with information sharing, right? You have to have that relationship built out and you have to agree that you will have that open path of communication.

Lerman: And certainly, when things go awry, which, but let's be frank, I mean that's going to happen. Things are going to have to change. You're going to need to be willing to hear those things from your supplier: Hey, what you're telling us to do is not possible. What can we do to redo that? Approaching these as a co-development partnership in both directions, that you're being honest with each other, that you're sharing information and really making the most effective version of your system that you possibly could, and being willing and able to roll with the punches, right? You're going to get negative results in some areas. How are you able to innovate both on the actual drug side with the delivery system side itself to overcome those. And thinking about [it] prospectively with your partner, these are possible outcomes of this. How do we look to the next step so that we already know how to proceed, whether we have positive or negative results?

Gotcha. And something that came to mind [that] perhaps you could illustrate — and you could illustrate it either way or both — and that would be [that] certainly there are plenty of moments along a product development lifecycle where something could either be critical to moving something forward and being successful or something could be a bottleneck or a breakdown moment. Can you think of particularly common or relevant examples where there's a tipping point one way or the other in terms of what the relationship or the things provided by a supplier might be in terms of, this is critical to moving it forward? And then, in this same moment, this could be a potential bottleneck or breakdown?

Lerman: In my experience, I've seen this happen with usability testing. Unfortunately, I've seen both sides of these relationships start pointing a finger at the other firm, saying, well, it's your responsibility to do these data. Well, that's not really an effective way to resolve this conflict, let's say. And really to move an entire process forward. The drug firm’s clinical team and development team certainly have the raw information about the drug and the patient population. The device firm certainly knows how the system is supposed to be used. This is something that you all need to work together to resolve effectively. And if you do not [have] a way to share or work effectively with your partner, you've kind of hit a major impasse, as it’s critical data needed to bring your product to market.

Okay, good. So, usability tests can be one. Any others come to mind?

Thorpe: Yeah, I agree. I think the other one could be post-market activities. So, complaints. If you have adverse events and complaint-handling post-launch, ensuring you have that relationship in place with your supplier, post-launch, so that those can be handled and those can be investigated and those can be remediated quickly so that you're not in this cycle of just constant rising complaints without a resolution.

Also, as you have design changes — post-launch design changes and lifecycle management activities —you also need to maintain that relationship. And that needs to be a partnership because things may need to change on the supplier and then, of course, on the documentation side from a combination product side. So, that's another example I think could be a tipping point.

Gotcha. And so, obviously, in what you're tracing in those examples, we're moving into the idea of controls or supplier controls. It's not only best practice, but it's also a regulatory expectation, and we'll talk more about that. But let's talk about that concept, both from the perspective of the product developer — the sponsor company or biopharma organization — and from the perspective of the suppliers. What does supplier controls mean, generally? And then from both perspectives, how should both organizations see their contribution to and responsibility for ensuring that whoever is going to scrutinize the process and the product believes that supplier controls were in place and solid.

Lerman: Certainly, this comes down to some of the core elements of your system. So, whether your critical quality attributes [CQAs], your essential drug delivery outputs [EDDOs], how are you linking those to certificates of conformity? How are they being relayed in your process output reports and your statistical process controls? How the entire ecosystem of how your inputs, outputs, specifications, how they all trace through and are not just you’re pushing them forward to your supplier, but also gaining back information to see problems prospectively before they hit the market or, god forbid, hurt a person. But also, make your system and your manufacturing process as efficient as it possibly can be — a really present, efficient, and direct means of providing direct oversight over your suppliers. But also, knowing that every product that you make together is as it was intended to be.

Thorpe: Exactly. And with that, once you've defined that, you also have to define — as a sponsor, you can't oversee everything, you can't be there a hundred percent of the time. So, you have to share that accountability of oversight. And you have to define ownership of who's going to be owning what part of those controls so that you're fully covered. So, defining that ownership, whether it's controls or even risk assessments that you have to do from time to time, having a tool like a RACI that we use in development, even something as simple as that, would be very helpful.

And then also, ensuring that your relationship isn't seen as policing. It should be a transparent back and forth so that both the supplier and the sponsor, their shared goal is that regulatory readiness so that if you've got an auditor that comes to your site, you're ready from all sides. So, that would be my take.

Good. And as I asked you before on the previous question about can you offer any illustrations or examples: Again, are there particular common moments in a development process where additional controls may need to be applied, so to speak, or revisited from either side? Are there typical places where this moment where the organization says, I'm going to have to apply some additional controls here, or the supplier organization feels like, oh, I'm not living up to what I need to demonstrate to “be controlled”? Any “for instances”?

Thorpe: Yes. So, there are examples of, if you've identified certain lot release tests, for example, that you want to perform or you want to have performed on your device, on your component at the supplier that you need for your product, but the supplier doesn't see it as a necessity. Implementing that and being able to work with your supplier to implement an additional lot control test, developing that test method, validating that test method, making sure it goes through the way you need it, and negotiating that because it is additional work for that supplier. I've seen that be a pain point in the past where the supplier says, well, we're doing the minimum that's required of us, but the sponsor says, well, we need this additional item. So, I've seen that be a pain point.

Lerman:  I've also seen an adverse event and complaint handling as a pain point for this because, ultimately, the sponsor is going to be accountable for that information. But it may be a little far-fetched for them to be able to meaningfully investigate the source or the root cause of the error. So, working with your supplier, not just in the, how are we innovating this together? But [also], in, when there are materials going back in. How do we investigate and how are we reporting and how are we maintaining compliance with regulation and providing information as publicly available as appropriate?

Gotcha. So, continuing on the supplier controls beat or topic here, let's move specifically into the regulatory expectations and guidances around that. And feel free to answer, obviously, specifically in terms of the United States and the FDA, but also if there's any distinctions or flavor to be added when it comes to outside the U.S. What are some of the guidances and expectations? And what documents need to be adhered to? What documentation needs to be surfaced, and so forth?

Lerman: Sure. Certainly, within the U.S., as I mentioned, Essential Drug Delivery Outputs: With the draft guidance coming out, there's been more clarity in what's expected in both pre- and post-market activities to maintain evidence that your system is functioning as it is and to make that roll forward.

But ultimately, all that rolls back up into, how are you aligned to [21 CFR] Part 4? How are you augmenting design controls in your system? And how are you building on decades of guidance and expectations to make sure that the system is GXP compliant? It's a really easy thing to speak in broad terms, but for individual systems, individual drugs, what does it mean for the individual components and materials, et cetera, to meet the individual requirements needed for that specific system? And there are countless resources out there. But, at the core, I would say certainly your basic ISO 13485, 14971: How are these core design controls and risk management approaches being implemented in our system so that the product holistically over its entire lifetime is being maintained in a safe and effective manner?

Great. Albana, anything you want to add on the specifics of the regulatory front?

Thorpe: I think Max got it. And I think, taking that into account as you work with suppliers, you should be maintaining your DHF [Design History File] per those standards — maintaining the DHF and the risk documentation for the standards so that you can be inspection-ready really at all times.

And as guidances are updated, embed that regulatory intelligence as updating into your QMS updates. So, there should be living documents that are updated every time something changes. And then, if you are finding any compliance gaps, don't try to find a workaround; actually fix it in your QMS. We see a lot of that.

Gotcha. Well, I'm going to move toward our last segment. And as I like to do in these, I like to open it way up and provide you an opportunity to offer perspective with whatever comes to your mind in response to the idea of looking out over the horizon, whether that's the near horizon or the far horizon. So, if there are any advancements to be made, any challenges to be addressed, any movement to be made, whether it's in how sponsor and biopharma organizations approach their supplier relationships or supplier controls, or whether it's the activity and approaches from supplier organizations: What would you point to as potential opportunities for advancement or addressing challenges and moving the dial forward from a positive improvement perspective?

Thorpe: I'll pick my favorite, which is improvement in data sharing. So, if we could move to some type of digital platform for sharing information between supplier and sponsor, whether it's in regards to QMS, any risk management documents as we go through lifecycle management or lifecycle support, or even complaint handling or anything post-market — that can really streamline the supplier controls and enable that transparency between supplier and sponsor. So that would be my top one.

Gotcha. Max?

Lerman: I would say there's huge opportunity for more global harmonization. As you're going in the United States, I know we spoke a little bit more specifically about that, but how does that compare versus going to the EU? Do I need a notified body opinion? Do I need to comply with MDR [Medical Device Regulation] and whatever else?

But the drug submission firms have worked in concert with various firms —I'm not going to attempt to list them all — to have a unified submission system. But that doesn't mean the data that each is asking for is the same or the means they actually can provide into them are the same. I mean, an easy one in the United States, it should be in English if you're talking to someone; that might be a barrier for some firms to jump over.

So, there is a lot of opportunity there because, at the end of the day, a drug which is safe and effective in one place should be safe and effective everywhere. How are we evidencing that, then working towards a globally accepted benchmark to how we set that standard.

Good. Well, Albana and Max, I want to thank you for joining me and sharing your perspectives on supplier management and supplier controls with our Drug Delivery Leader audience. And to that audience, I want to thank you for joining for another episode of In Combination. And we'll see you next time.