Quality Grind Podcast

Technology Transfer Part 3: Executing the Transfer

• MEDVACON Life Sciences • Episode 14

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In this episode of the Quality Grind Podcast, host Mike Kent and Medvacon consultant Kim Lim round out their exploration of Technology Transfer, identifying the critical strategies that foster a smooth execution process. Discover the value of thorough preparation, the significance of quality agreements, and the role of process performance qualifications (PPQ). Emphasis is placed on maintaining transparent and frequent communication between sponsors and contract partners, as well as fostering strong interdepartmental relationships. Tips for managing documentation and data are also highlighted to prevent pitfalls and ensure the creation of high-quality products. Perfect for anyone looking for actionable tips and expert advice!

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Ep 14 Technology Transfer Part 3 - Executing the Transfer w/ Kim Lim

Jessica Taylor: [00:00:00] This is the Quality Grind Podcast presented by Medvacon. Conversations that go beyond compliance. Sharing insights geared toward helping you navigate the everyday grind of regulated life science industries. Here are your hosts, Joe Toscano and Mike Kent.

Mike Kent: Welcome back to The Grind, everyone! In part three of our series, Kim and I discuss critical strategies and tips for executing a successful tech transfer and how to put all of your diligent planning into action.

Let's switch gears here a little bit. We've talked about what goes into really good preparation. Let's talk now about, all right, now we're ready to really do this from an execution standpoint and making sure that it's working the way that we all intend it to work, not just the sponsor from the development side, but [00:01:00] also the contract partners. 

Where do we start with that execution process? 

Kim Lim: Yeah, absolutely. So, once you understand and identify the key players and in the process, it's really important to have consistent and reoccurring meetings and put together a team charter. You're now a team. Understanding what your objectives are and how this is going to be executed. Typically, the contractor usually has a project manager that helps facilitate these things, but having communication on a regular basis is really helpful.

Having the deliverable of a protocol. So that takes a lot of time. I mean, I just can't emphasize enough. If it takes 6 months to get that protocol written and all of the key elements in there, and understanding whose [00:02:00] expectations are set and met, that upfront work just goes miles and miles down the road in the process.

That includes when Quality gets involved, when Regulatory gets involved. Asking Regulatory what their requirements are very early on and adding that into the protocol. And then once that protocol has been approved by all entities, executing on that. Going through PPQ runs, understanding what your process is looking like. Making adjustments at that point, we're still, you know, trying to figure this all out, right? We're kind of in that living together stage, right? Whose toothbrush goes where? And, uh,

Mike Kent: Here we go. 

Kim Lim: That's right. Yeah. So

Mike Kent: Well, I'm going to be the difficult partner here. Can you go back and explain what, you used a term " PPQ".

Kim Lim: Yeah, so Process Performance [00:03:00] Qualifications. So really understanding (okay) from soup to nuts, from the beginning to end, how you're sourcing your materials, going through receiving your materials, putting all those materials together for the manufacturing process, going through your developed manufacturing process at this point, and then verifying at the end that you're getting the yields and the product that you want at the end.

Typically, these are run three or four times just to understand what your process is looking like and that it's reproducible and repeatable. I mean, this is where we're at now. 

So once the tech transfer protocol is done, you're really in the verification phase of what your manufacturing process is looking like. Not to say that there couldn't be adjustments at this point, but you want to be able to iron out all those specifications to get your end product during these PPQ [00:04:00] runs. 

Mike Kent: And the consultant in me, and I'm sure you'll echo this as well, feels compelled to say all of that early upfront work, all of that upfront process characterization and the piloting runs that you mentioned, the engineering studies at the contract partner, really to get a sense of how things do behave in that different environment are going to be absolutely crucial and save you time if you get "good" results or "different" results or God forbid, "bad" results, whatever the adjective is. Having that information to go back to and use to help assess what may or may not have happened that led to that can save you time, money, energy, et cetera. 

So is it fair to say that, and you mentioned putting all the ducks in a row in six months worth of time as maybe a baseline or maybe a benchmark in getting that [00:05:00] protocol together. 

Kim Lim: Oh, absolutely. I mean, this is at least a good discussion around what requirements are, what specifications are, what ranges are we willing to live with, what can we stretch out a little bit, what's critical, what's not critical, those kinds of conversations all happen during the protocol vetting process.

Mike Kent: Okay. And you mentioned a quality agreement. How does the quality agreement differ from the actual protocol and what advantages are there in having that quality agreement up front for organizations in terms of process and communication and decision-making? 

Kim Lim: Quality agreements are very important. Most contract entities are going to require it from you because it's a clear, clear definition of who is responsible for what. 

Is the sponsor responsible for providing materials? Is the vendor or the contractor [00:06:00] responsible for providing materials? Is there a particular vendor that the sponsor requires you to buy from? Those are those things that are very well vetted out in a quality agreement. 

And then, of course, on the back end, it's part of the quality system, too. So, who is going to be signing off on deviations? Who needs to see the deviations? Who needs to see OOS's? Who needs to sign off and approve those? Those decisions need to be made really up front. So it's a clear, clear, clear roles and responsibilities that is really defined. Also, it really just allows everybody to do the work that they need to do within the construct of this.

So, it's super important. It's very important to iron out these details. I can't emphasize enough that there are several instances that I've been in as a consultant where the quality agreement is kind of almost left to [00:07:00] last right before the large scale manufacturing run. And then it was like, well, I thought you were going to do that. No, I thought you were going to do that. And it is true, the sponsor is ultimately responsible for all of this. So you really want to know what your contractor is doing for you and on your behalf. So things like, are they reporting OOS's to you? Do you need to know that? Do you need to put that in your quality system to understand what your process is? So those definitions within the quality agreement are very important.

Mike Kent: It seems to me, and what just bubbled up was, we started talking about execution and we're going back to preparation and I don't think it's an accident actually. And I'm really glad it came up that way because so many of these things, as you so eloquently said it, you keep coming [00:08:00] back to all of these needing (yeah) to be worked out up front, or at least discussed, so that we understand what the nature of the construct is going to be. Who's going to be making the decisions based on what information? How is all this going to go? The more that you have that ironed out, you're not figuring it out when the deviation occurs and saying, "Well, we've got this deviation",

Kim Lim: Right. Right. Yeah.

Mike Kent: And all of a sudden your clock (yeah) is ticking because that contract manufacturer had one week for you and their next available spot is seven months from now. And if you don't have things nailed down, you know, we keep coming down to that timing. That's kind of the reality. 

In terms of that execution, what from a sponsor standpoint can go towards making sure the contractor's or the contract facility's execution [00:09:00] goes well? What level of oversight is appropriate? What might be too much and what might be some things that people often forget that they shouldn't? 

Kim Lim: I can't emphasize enough that you're forming a relationship with your contract entity. You know, these are people, too. Let's just have conversation. Let's just have communication. It doesn't need to be, "I need to be there all the time to see you how the process is going." But, you know, there should be communication about, "Oh, what happened today is we didn't get the yields that we were looking for. We're doing an investigation. We'll keep you informed about it," and kind of letting that go. But again, it is your responsibility as a sponsor. So it is really up to you how involved or uninvolved you want to be in the manufacturing process. I think that's up to the discretion of the sponsor, but knowing that you have hired this contract [00:10:00] entity to act on your behalf, then you need to allow them to do that, as well. 

So, I think communication again is super key in this situation where you're telling each other, talking to each other on a regular basis. You're really trying to work out what is the best process for you. So, we all want to create a good product that helps people on the market. So let's get there. And how do we get there?

Mike Kent: How much does the phrase "Trust but Verify" come into oversight through that execution? 

Kim Lim: A lot. I think that you have to see how they're going to do it. This is where engineering runs come in key. You can see how they're documenting things. You can see who's involved in the manufacturing process. 

And then when it comes down to the PPQ runs, do you need a person in place there? Do you need to be there for [00:11:00] what the manufacturing process is doing? Are you just there as a Quality representative to move things along? If there is a deviation and you're on the floor right there and then, you can make that quick decision to say, "Oh yes, we can move forward," or "no, we have to stop the process now."

So, I think having that good relationship with your contract entity, I think that goes a long way in these situations.

Mike Kent: So how do you know that it's not working or not going well?

Kim Lim: Yeah.

Mike Kent: Are there signals from either side? And here again, I'm thinking I need to course correct. Are we talking dating or are we talking Tech Transfer, right? How do we know that things are as they should be, or when things are starting to potentially slide off the rails?

Kim Lim: Yeah, I mean, pitfalls or secrets, secrets or pitfalls. Like you're not informed, somebody hasn't been told, you [00:12:00] get a last minute warning. Just surprises. 

So I'll give an example of, you know, again, we, a client was promised like, we are going to do all these analytical development tests for you. We're all going to do all these release tests for you. And then all of a sudden, a week before the manufacturing run, "Oh, we can't do the potency test. We don't have a validated method for it. And now we have to outsource it to maybe another one of our partners or another one of our entities. But now you're going to have to go and qualify them. You're going to have to audit them to see it." 

So, again, that upfront and being honest about what you can and cannot do goes a long way, because if they had just said in the beginning, you know what, we don't have a qualified method, but we do have a trusted partner that you could qualify to do this. We could have done that eons ago, and this would not hold up the process, right? So I think [00:13:00] again that idea of communicating, being very honest with each other. Yeah, I feel like we are talking about dating again.

Mike Kent: Here we go.

Kim Lim: You know, we're all humans, right? These are all human relationships. So, that really is helpful. Like again, secrets, that's really bad. 

And then it could go the other way. I had another client who, they had a contract manufacturer creating their product. Just as a courtesy, because they got very, very small yields from the initial engineering run, they opened up their OOS system and their deviation system to the customer because they really wanted to be honest about what the investigation they did looked like so they could glean information from that, and maybe trace it back to a point in the process where things may have gone [00:14:00] wrong.

So I think the communication can go both ways. So if you can over communicate with your client without compromising your own contract entity, then do so. I think that created a stronger relationship between the sponsor and the contract entity, honestly. So it can go both ways. 

Mike Kent: Yeah, that transparency is absolutely key. The instance you bring up causes me to go back to my example from earlier. Let's say that something happens down the line, and something does go wrong, off the rails or differently than we expect or differently than what was seen in the development process. There may not be an awful lot of development history or development data there really to explain what may or may not have happened. Now you don't have any [00:15:00] information about that particular event, and maybe not even knowledge that it may have happened earlier on to try and correlate it. So now you're 0 for 2, and if the contractor doesn't make the sponsor aware that this has happened because it's just an engineering study, and there's no commitment to do that, and we're busy, and et cetera, all the things, then everybody loses. And then the stakes when they get higher are based on, well, we haven't seen any issues yet. Oh, but we have, and we just don't have those up on the surface to inform our decisions. And that's when I get really nervous about these sorts of things going on and there are surprises, right? But I would imagine it happens. 

So how do we navigate that next step and continue that relationship after maybe the main, the Verification batches [00:16:00] have been run, the protocol has been executed, everybody's reviewed and signed off on everything, and it's now in the archives.

Kim Lim: Actually, I do want to go back, Mike, to something that you said, and it made me think that, you know, this is not only just between a sponsor and a contract entity, we're talking about between interdepartments, too, like from Development over to CMC and then CMC over to your internal Manufacturing, right? Those relationships have to be very strong and the communication has to be strong. 

So, if you have a manufacturing supervisor that's not being upfront about, "I have to maintenance this machine, but we scheduled you for a run, and you know, things may behave differently than what we thought before because we're under maintenance." That's a breach in the communication and trust that you would have within your own organization, let alone another contract entity. 

So these relationships that we're [00:17:00] talking about, I think are very pertinent to within the company itself, too, within a large organization that could potentially have all these departments within itself, too.

So just want to make that point. And then...

Mike Kent: Kind of making sure your house is in order before you...

Kim Lim: Sure! Ha ha ha ha ha ha... 

Mike Kent: I, I think I know how we're going to theme this particular episode. We didn't plan it this way, folks, but, you know, when something happens like this, you just gotta run with it. So... 

Kim Lim: oh, no, not at all. Not at all.

Mike Kent: I had to, had to interject. Yeah. 

Kim Lim: And then to answer your question about what happens next is really reviewing and understanding what happened during those engineering runs. And what are we going to do moving forward? Do we need to adjust specifications? Do we need to [00:18:00] adjust ranges? Are you bringing in new equipment for this manufacturing process? Are we going to be doing validations around that? What does the large scale look like, because that's the next step, right? Okay, now we've proved that we can make this stuff. Can we make a lot of this stuff? So, what does that entity look like and what can we do to get there? 

So I think it's this again, continued relationship, like you're growing now, right? So, you know, maybe there's like kids on the, on the horizon... 

Mike Kent: Talk about complicated.

Kim Lim: Right.

Mike Kent: I think we may have to shut down this counter-discussion. We're going to get ourselves in a hell of a lot of trouble. No, I absolutely understand.

Kim Lim: It does. It gets more complicated. Yeah. And you're evolving. And, you know, we're talking about years of a [00:19:00] relationship. We're not talking about, you know, weeks or months. So, are there key people who have now changed positions? Are they in different, um, in different parts of the company? Are they not with the company anymore?

So all of these things need to be a checkpoint at this point to see where we're at and then kind of plan for the future of what that looks like.

Mike Kent: So along those lines, the example of someone leaving the organization, whether it be on the sponsor side of the contract side, really piqued my interest. There's a lot of knowledge that goes with that individual. So how do we continue then the process?

Kim Lim: It really is a team effort and creating that team regular recurring meeting in the beginning. Having rigorous meeting notes so you know where decisions were being made and who had [00:20:00] spoken about what. Enlisting other individuals from the company to see if they have the technical expertise to pick up where this person has left off.

And also being pretty up front about it, too. It does no good to a sponsor if a contract entity knows that this person is going to be leaving within 3 or 4 months or retiring within 3 or 4 months. So, you can't help somebody winning the lottery. But I think prepping for what the team will look like in the next six months and can they stay the course of all of that goes a long way. But again, documenting, documenting, documenting as much as you possibly can during the entire process. Whether it's the lab notebooks we're going back to, to you know, what are the results that we got from the engineering runs and the test protocol, like that. We want to have all of that historical knowledge that are, available to [00:21:00] us.

Mike Kent: So with your experience, having done this on both sides of the ledger, are there particular strategies or tactics or tools that you've seen work really well for sponsors and contract organizations to capture that documentation, to capture that knowledge, if you will, in a way that is effective, efficient, but not overbearing? 

Kim Lim: Simple, simple tools. I'm even going to pare this down to usually if I have a meeting with a potential client, just a quick summary email of what we talked about and then an acknowledgement from them. "Oh yeah, I get this. These are the action items that we both committed to."

So it doesn't have to be like this huge formal process of let's get a scribe in the meeting, let's take, you know, vigorous notes about things. But again, [00:22:00] acknowledgments from both sides. Oh, this is what we talked about. This is what we committed to. Yes, I heard you, I'm committed to this, and just follow up. So I don't think it has to be elaborate, but I think email is a great logging and scribing entity for yourself, and quick and easy, right?

So quick communication and it's in a server forever, so you can go and look it up later on, too.

Mike Kent: So that level of organization within the actual formal documents, is there value in providing annual project reports or some sort of summary documents at different points along the way? Maybe the stage gates that you mentioned earlier. Are there those sorts of tactics? Can they be good sources of information? Even later on after the [00:23:00] actual transfer, as the relationship continues, is that something that could hold some value?

Kim Lim: Yeah, I think that goes back to the team charter. And when you say in the beginning, what your objective is and what your mission is, and then how are you going to do that on a project-based level? So, very high level at one point, so you're going to do these checkpoints and check in and do documentation on that to just see what the outcomes were. 

And then, constant review. Let's keep having review meetings about what did we learn, what didn't we learn? What didn't go well, what did go well, how can we communicate better? Because I think that evolves over time, right? Maybe it is a recurring meeting, but now it's not so often. Maybe it's a monthly meeting now. Maybe players have changed, maybe new projects come up and then those teams form on the side. So it's [00:24:00] different people now that are part of the process. 

But I think really again, going through a structure of putting together a team charter, knowing what your mission is, knowing what your objective and a very skeletal 'how we're going to do this' and when those checkpoints are is very important in the beginning.

Mike Kent: Yeah, it makes a lot of sense. And for those of us who are rolling our eyes of, Oh, I've got to come up with a mission statement...

Kim Lim: But it can be just so simple, right? Make good product.

Mike Kent: It really can be, yes. There you go.

 So, yeah, a person like me would walk into that meeting and say, all right, well, I hate to be the thorn in everybody's side, but, define what "good" is. And then all of a sudden you've got everybody rolling their eyes at me, which has happened once or twice or... Anyway, I digress.

Along those lines, the information and the [00:25:00] process around the interactions and agreements and decisions are one thing. And you've talked about some strategies for those. 

But the last piece of that is the data, the information, the records. So who owns those? How do both parties make sure that it's clear who's capturing what, who's maintaining what, and how should organizations go about maintaining that data?

Kim Lim: Sure. So this is where the quality agreement is key, where it defines the roles and responsibilities for each of the parties. So again, I can't emphasize enough, even if you are a sponsor that is a company of five people and you are outsourcing everything. Your ultimate responsibility is the product itself. So you are, the buck stops with you. [00:26:00] Whatever makes you feel comfortable of the control you have over the process and the documentation, that is what you need to have, because you are going to be subject to FDA scrutiny. So that's definitive.

And then again, choosing the partners who are capable of supporting you in that. So, you can put into the quality agreement what is proprietary information, what you own versus what the contract manufacturer owns, how long they need to keep your documentation for, what you're able to see on a regular basis. Maybe you have to come in and do an audit on them on a yearly basis if they're a critical vendor for you and you have to be subject to all of the documentation that you've produced over that period of time.

So, that really has to be set up front in the quality agreement. That's [00:27:00] where it really belongs. And, I'm sure as a legal representative, they would really want to see a lot of this in the actual contract with the contract entity, too, just for legal purposes. How things are going to transpire if there's a breach of the contract and what that looks like and who is involved in that and, what monetary compensation comes from that, too.

So I think these are all pieces of those upfront documents that you have with an entity before you even get started.

Mike Kent: What comes up for me is begin with the end in mind. Plan for various outcomes, no matter how likely they are. You mentioned it earlier, taking a risk based approach to a lot of these processes and a lot of these activities. And I think having an [00:28:00] understanding of not only the risk tolerance of the sponsor, but the risk tolerance of your contract partners is equally important. And that will come through in the quality agreement. 

Kim Lim: Those can morph over time, right? It's not a standing document. You can, it's a fluid document where depending on the phase and stage that you're at, maybe things change. So, maybe there's a quality agreement for just phase one and there's another quality agreement for phase two activities. Then there's a quality agreement for phase three. And I think that's appropriate for contracts, too. Maybe you have a development contract with your partner, and then maybe later on you have a manufacturing contract with your partner. 

So, these are all fluid documents that don't have to be, "Oh my God, I have to think about all of this all at once right now, and that's the end of it." We can change these over time.

Mike Kent: That's a really great point. You know, I'm guilty of it [00:29:00] in this discussion, thinking about all of the things, and okay, how do we put a bow on this and wrap all of this information up? We don't necessarily have to boil the ocean right up front. We can take little pieces and focus on those chunks.

And there again is another reason why your suggestion of having a sense of how your process is going to go, what your life cycle looks like, and the expectations that you have as the sponsor through that life cycle can go an awful long way. I think those are great suggestions. 

Kim, of all of the things that we're, we've talked about, and... Part of me really hates having to do this, but at the same time, I'm really curious. There are some common themes that come up in discussion. What to you are the most important key common themes for both sponsors and contract partners to keep in mind as they [00:30:00] navigate this process? Maybe not feeling like you have to boil the ocean right up front is number one.

Kim Lim: Communication. Communication is key. Transparency is key. Like you said before, really understanding what each is capable of and what we're willing to do. And then learning as you grow together, knowing that it's a partnership, and if you're truly looking for a contractor, then that's fine. But, don't forget, this is your development process as a sponsor. This is your product. I would like to trust it with a partner. I would think other people would, too. So I think forming relationships is really important when getting to the end goal of creating a good quality product.

Mike Kent: I'm just going to make an observation from a chemist to an engineer. As with a lot of the topics here on the [00:31:00] Quality Grind Podcast that we discuss, what really determines success versus other potential outcomes is how people connect, how they work together, how they continue to build and strengthen those relationships, and the communication that happens through that process. And that's one of the things that as scientists and engineers, we can struggle with. Okay, people are people and we'll just talk, and we'll just, everything tends to be very matter of fact, right? But in that process, we can sometimes lose sight of the details that may matter. And focusing on the science is absolutely the number one thing.

I think what we've illustrated today are the benefits of how to connect people that have a stake in the overall process, questions to ask, things to [00:32:00] align to, agree on, and how to proceed and focusing not only on the technical aspects of things, but how things are going can lead to success.

Kim Lim: Oh, absolutely. Yeah.

Mike Kent: Well, we realized that we were going to take a big bite off of another big apple. And this is a really important topic for industry, especially in the last decade or so, where we see so many more organizations popping up out of University laboratories, they come up with something, they go into a virtual organization. And now how do we get people to do this? 

So we hope that everyone has enjoyed this episode of the dating game, I mean the Quality Grind Podcast, and we invite you to like, share, and comment wherever you're getting your podcasts and share your comments with us, engage with us at our website, by email, et cetera. 

Kim Lim, it's been fantastic having you. This has been a tremendous discussion. [00:33:00] Thanks so much for being here on the Quality Grind Podcast!

Kim Lim: Thanks for having me. 

Joe Toscano: If Medvacon can help you and your organization, we're happy to do so. We specialize in the following areas: Quality and Compliance, Validation and Qualification Services, Project Management, Tech Transfers, General and Specialized Training Programs, Engineering Services, and Talent Acquisition. If you have general questions as well, feel free to give us a call at any time.

We can easily be reached at 833 633 8226 or via our website at www. medvacon. com. Thanks so much, and we look forward to speaking with you.

Jessica Taylor: Thank you for listening to the Quality Grind Podcast presented by Medvacon to learn more or to hear additional episodes, visit us at www. medvacon. com.