Quality Grind Podcast Episode 11 | Technology Transfer Part 1: Preparing for Success

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! Mike Kent along with you today flying solo, as my cohost, Joe Toscano is out helping clients and saving the world, putting out fires with his own unique fire extinguisher. You all know the drill.

But we’re not alone today, we have a very special guest. Kim Lim is here to help us talk about Technology Transfer, whether you’re on the sponsor side or you’re on the contract facility side, that a technology transfer works for you, can be successful, and ultimately achieves the outcome that everyone wants.

Kim Lim [00:01:00] is a biotechnology consultant with over 30 years experience in Validation, Technology Transfer and Operations Management. She founded and operated Ultimate Labs, a contract testing laboratory supporting small startups to large corporations. Kim holds a BSE in Bioengineering from the University of Pennsylvania, and an MBA in Operations Management from Columbia Business School.

Kim, it’s great to have you here on the Quality Grind Podcast. Welcome!

Kim Lim: Thanks for having me. Such fun.

Mike Kent: Well, you say that and we shall see, right? I’ll ask you how much fun it was at the end. That is one of our goals. I hope that we can have a lot of fun during this discussion, as well as tackle this big topic.

So one of the things that we really love to do with all of our guests that we bring on is get to know them a little bit. Curious if you would provide our audience with a sense [00:02:00] of who you are, how you came up through the ranks, what you’ve been up to in your career. And more importantly, why did you choose this line of work? What drew you to doing this for a living of all the possibilities?

Kim Lim: Funny you should ask that, Mike. So, I’m actually a bioengineer by training. So nerdy engineer going through college and one of my senior presentations was about how the FDA is involved in what the regulations are around medical devices. And really, the project that I was doing for senior year was building toys for kids with cerebral palsy. So, what were the regulations around that? Had to do this presentation for school. So really kind of fell into the regulated space, which is really interesting.

Right after college, I went into [00:03:00] validation, which is really trying to keep facilities and processes in the regulated space for pharmaceuticals, medical devices, biologics, and such. Earned a Master’s in Operations Management during that time, and then landed in San Diego working for a couple of operating companies that were making pharmaceuticals and medical devices. And it was an auspicious day when I was in a room full of consultants and complaining about all of the support services that we needed, such as environmental monitoring, water testing, you know, things that a quality control laboratory need to do to help out with the validation process.

And somebody had said, “You know, you complain so much about this. Why don’t you do something about it?” And I started Ultimate Labs and,

Mike Kent: Ah [00:04:00] ha.

Kim Lim: Yeah, and right at the economic downturn, which was super interesting because a lot of companies were downsizing at that point in time and outsourcing a lot of these tests.

So we did fairly well during that period of time, did that for 11 years. And so, sold the company to a larger conglomerate to make it grow and be better. And here I am today back to consulting again. So I, my brain doesn’t turn to mush. yeah, so

Mike Kent: to go to mush. It must be part DNA, right? And you got to start right early on, as you said, in the regulated space. So was that your choice?

Kim Lim: Really, the program [00:05:00] that I was in at University of Pennsylvania was a pilot program for bioengineering. So they didn’t have bioengineering classes per se. They really mishmashed all the engineering classes. So we took a lot of chemi, we took a lot of structural engineering. So, and with a bio, like a biological slant.

So mechanics class had biomechanics versus straight mechanical engineering, and then a piece of it was to get real world experience. So as a senior project, you would have to pitch to investors what your product is, how you vetted it out and knowing that, you know, part of what we do as medical devices, and even toys for children, it’s regulated by the FDA. So, this was something, a topic that by default I was nominated to do the research on, [00:06:00] and kind of went from there.

But I had found it interesting that moving into the validation world, it was a great experience to be a consultant, going to different companies, seeing different products, seeing different iterations of products, pharmaceuticals, therapeutics, medical devices, how people are challenged by the regulated industry.

So I had a myriad of clients that were either under a consent degree or they’re about to apply for an FTE filing or an ND filing. So it was just a large and wide range of experiences during that time that I was consulting very early on.

Mike Kent: And, as you said, set the stage for everything that came next as a successful laboratory owner, contract laboratory owner, and successful consultant. So those two pieces, I think, really position you very strongly [00:07:00] to be able to talk to this from multiple perspectives.

And that’s one of the things that I’m hoping to cover during our discussion today. Really, there’s a lot of different people that are involved, and we could go down a list. And in most places, there’s a list of the key players in this process, and we’ll get to that as we move forward.

But really, what we want to try and do is understand how those pieces fit together and what goes into that. into making that a successful connection, not just from the technical side of things, but how do we engage folks? How do we keep folks engaged in the process and make sure that folks are involved as much and as early as possible.

So with that, Let’s back up just a touch and talk a little bit about technology transfer. I’d like to understand your perspective of what [00:08:00] technology transfer is, what the common definition, if you will, is, and then what is it really from your perspective?

Kim Lim: Sure. So, you know, traditionally technology transfer is really a scale up, whether it’s within yourself, within a company, or you’re going to transfer that over to a CDMO. So we’re going from the development phase into a more GMP, GLP phase. You might be doing your phase 1, phase, um, tox studies that you want to start gathering safety data on for a submission. So that’s kind of where we’re at for technology transfer. And there are certain gates, right? So there’s going to be the early stage gates and then the late stage gates when you get into full scale manufacturing and GMP manufacturing, as well.

Mike Kent: Okay, so what are some of the things during that early [00:09:00] stage process? Are we talking about pre phase one? Are we all the way back into early research? You know, do we have the, the time, the resources, the dollars, the capacity, the bandwidth, et cetera.

When should they then start thinking about starting this process?

Kim Lim: Yeah, so definitely sooner than later. Even so far as when you’re going through the development phase, you’re sourcing materials, you want to choose vendors who can stay the course of time with you, right? I’ve seen many, many times where vendors are chosen because of a relationship. They are very small entity. And then when it’s time to scale up, they’re not able to scale with you. Then you have to resource and re-qualify vendors, re-qualify materials. So that’s a whole gap in time that you’re going to waste if you don’t think about these things early on. [00:10:00]

I also think that If you have a concept that you’ve developed and it’s working very well on a small scale, it’s really good to look at tech transfer to a really medium sized scale of what your process is going to look like. And then, you know, thinking about what is going to be on the large scale. So for an example, in the biologics world, like we work in like very small bioreactor volume. So, you know, maybe a 10-, 20-liter while you’re in the development phase. The second phase would be in that kind of 250 range to see if we can get the cells to grow at that expansion rate.

And then, you know, when we’re going into full blown manufacturing, making lots for GLP or tox or even the initial PPQ lots, like we want to be in like a 500-liter range. So knowing that you have these stage gates for your particular process, like, what would that look like? And then bringing those partners in and bringing that tech transfer in [00:11:00] as early as possible, that would be the ideal situation.

And I can’t emphasize more: communication, communication, communication! Like, you just keep talking to people so everybody is on the same page.

Mike Kent: Yeah, there is no such thing as over-communication, especially early on, right? The more information people have, the more informed their decisions can be, and the more informed their input can be.

There’s a sense that technology transfer is only internal to external. You’ve got something and you’ve done your development work. And okay, you’re going to throw it over the wall, figuratively speaking, of course. But you’re going to pitch it over the wall to a CDMO, a contract development manufacturing organization, or a testing lab to scale up or a contract lab to scale up depending on your application. [00:12:00] And I’ve heard people start to talk more and more about tech transfer being more of an internal process early on where you go from that 5 mg scale or the 1 mg scale to 5 mg and you go from 5 mg to 100 mg or the 10 liter reactor to 50 mil or a 50 liter reactor. What value, if any, is there in thinking about the development process as a series of small internal technology transfers? Does that gain you any leverage later on?

Kim Lim: I have a great example for you in regards to that. Having these conversations within your development group early on is an excellent idea. Because you will start getting [00:13:00] folks involved from potentially CMC, Regulatory, Quality, in those early conversations about like, what do we need to do to prepare when you’re ready to push the product to its next phase, right?

So let’s take for an example, if you have a small molecule drug, and you have an 80 milligram potency at that point, and you want to change and do some studies around a 20 milligram potency or a different kind of, iteration of it. So this in itself is a small development project, correct? We’ve gone through the process of filing an NDA, getting the approval for the 80 milligram, but now we’re going back to see if we can do it with the same process with a 20mg potency.

This is where that comes in, where things can be smoother if we have early on conversation about, oh, what is the role of CMC at this gate? Who is going to [00:14:00] be doing the testing in our analytical development department? What are the resources that we’re using for vendors for materials for 80 mg? Does that apply to our 20 mg? All of those questions coming early on makes for a much smoother process and probably a quicker filing for you in the long run. So, I think it really does behoove companies to do small development groups and small development stages, and moving it through your internal departments.

Mike Kent: That’s great. And even from a single process where you’re just starting to get a sense of what’s there, what works, what doesn’t work, etc. When you move into that larger space of that larger capacity, it may be the same people, it may be largely the same process. But I think there’s some tremendous value to ask some of those additional questions that may be related to [00:15:00] technology transfer. And how are we actually going to do this and figure it out?

And that’s not to say that organizations just go in and do it willy nilly. I’m sure that everyone has those discussions. The benefit here, and it may scare people, and when you mentioned having Quality and Regulatory and folks involved in the discussions early on, I could feel the sense of part of our audience saying, “Wait a second, we’re still developing, we’re still tinkering.” And, you know, there’s a genuine I won’t say fear. Others might say fear, but there’s a level of anxiety that comes in with getting those folks involved. And maybe that’s something we can touch on here in a little bit.

But having those discussions and getting things, here we go with the GMP talk early in development, getting what you’ve done documented and documented well, what are those [00:16:00] parameters, making sure that you have access to the data that you’ve generated. That it’s of high integrity, that you have a high degree of confidence in that information and data that you can go back to and retrieve it if you need to. Now, there’s 1000 different reasons why that can and should happen, but mainly so that any decisions that you make later on down the pike, you can always trace back to, all the way back, and have data and information that’s been captured, that’s accessible, that has a high degree of integrity, that’s been evaluated to a certain degree to make sure that that is the case.

Are all of those things valuable to setting yourself up for future decisions and being able to provide information either internally or externally through the transfer process later on?

Kim Lim: You know, in fact, the ICH guidelines are really pushing the [00:17:00] idea of Quality By Design in the guidelines, and really starting it within the beginning of a product life cycle to really think about what you’re going to be doing long term down the process. That’s built in to the guidelines as well as, you know, risk assessment and doing risk analysis throughout those phases. So, just to waylay the concerns of the development people. We don’t want to I know

Mike Kent: Here

Kim Lim: don’t want to hinder the science.

Mike Kent: Yep.

Kim Lim: Yep, you’re right.

Mike Kent: them

Kim Lim: We don’t want to hinder science at all, but let’s take a risk based approach. So maybe in the early stages you have a range of a specification that’s quite wide, or maybe it’s “As Reported” at this point in time.

And then when you get to Phase One, we kind of narrow that down to like it has to be less than, or it has to be greater than. And then when we get to Phase Two, when we’re starting to validate methods, we’re getting that range even tighter. So [00:18:00] it’s between one and ten at this point now.

So, Quality is by no means interested in hindering the science behind all of this, but really kind of giving a guideline of where we should be at a different stage gate. So when it comes down to the Phase Three studies and we have to have a very tight specification and very good data to back up those specifications, it’s an easier process to do that. And then we’ve done all of the work and documented all that work to support all of that specification data. That’s kind of the idea of Quality By Design in a nutshell.

So again, not to hinder the science, not to hinder the discovery, but really just to understand where you’re at and take a risk based approach to all of this.

Mike Kent: Yeah. And I’ve heard it said lately that It’s not necessarily Quality Assurance in the [00:19:00] Development process. What it is, is really good, sound, robust science, and all the parts of science.

I can remember being a chemist in college and the worst part about all of my lab classes. Lab was so much fun for me, so much fun! It kept me going in science, but the worst part of it was always doing the write-ups. And I hear that all the time.

I know everybody hears that all the time. “You know, we’re doing the work and we’re generating the data and we know where it is and we know what the conclusions were and we know that it worked and we knew what didn’t work. And so we made these decisions.” And more and more, there is so much value in understanding and really having objective evidence to support those discussions and those claims.

 I had a client who had spent three [00:20:00] and a half years bringing a really, really solid product to mid stage development. And they went back after getting a result in the clinic that didn’t make sense and traced everything back to first principles, the early, early research work.

Mike Kent: And what they found, unfortunately, was that the data that was captured in the early research phase did not have as much integrity as they would have hoped, and some of the conclusions and decisions that were made based on that information were not necessarily documented robustly. People had left the organization. They didn’t really have an opportunity to understand why the decisions were made that were made. Was there more information? Was there a [00:21:00] misinterpretation of what was there? Because they went back and added up two and two and got seven instead of four.

But if you’re going to then invest millions of dollars into a technology transfer because you have data and have information about a material or a product or a device that you think works based on the information that’s there. What I hear you saying, Kim, is things like Quality By Design and expectations now that these sorts of principles are adopted earlier on in the process.

There’s an example of where had more rigor been applied potentially in that early situation may have eliminated or prevented that failure in the clinic.

Kim Lim: Potentially. Potentially. Yeah. And you don’t want to get down that road so far and have to trace back that far [00:22:00] too, right, to find out what happened in the beginning that now affects what your process is today. And I think most people don’t understand how critical that is, right? That everything, every step is critical.

It’s not that we go through “mad scientist phase” and then, you know, it’s all of a sudden we’re super serious about GMP manufacturing. It’s a gradual process. And, you know, everybody is responsible for quality and good scientific methods. So I agree with that. Yeah,

Mike Kent: It feels like we’re setting a really good foundation for being able to set our feet when we want to hand things over to that contract partner. We know that we’ve got a really good foundation and that’s a big part of it. Would you agree also that that is a potential risk for why tech transfers don’t necessarily go as planned or don’t [00:23:00] achieve all of the necessary outcomes?

Kim Lim: Oh, absolutely. And one of my biggest pieces of advice about doing a tech transfer to a CDMO or CRO or a CMO is really have this partner vetted out and bring them in to your development phase.

 Really to have those early discussions about setting expectations, right? What do they need to see in a specification? Who’s in charge of setting the specification? Who needs to be in charge of the analytical testing? Who has those means available? Does the sponsor have that available? Does the CDMO have that available? Knowing that you can tailor your development process to be as efficient as possible. So you’re working on the science and they can be working on, you know, those residual release tests for you, or, you know, vetting out as scaled up process for you, knowing what may be [00:24:00] coming down the pipe.

So I really encourage creating and developing very good relationships with your partners and bringing them early in the conversation with you.

Mike Kent: So from the sponsor’s perspective, who on the sponsor side of the equation should be involved in those discussions and should be actively participating in sharing that information or making those decisions with the individuals at the partner? And who on the partner side should be participating in those discussions?

Kim Lim: Yeah, so I definitely think it depends on the sponsor and it depends on the contract organization that you’re going to be working with, what their capabilities are.

At a minimum on the sponsor side, you want to have Development / CMC involved in the technical piece of it. Have some kind of Quality / Regulatory [00:25:00] representation for you, as well. And then if you do have these very involved test methods, have Analytical Development, Chemical Development, in on these conversations, as well.

On the CDMO or CRO side, you want to just see what the breadth of what they can do are. And I can’t emphasize this enough. Really, really get a handle on what their capabilities are.

You know, and I know, I mean, it’s a sales pitch, right? They want your business. They want you to work with them. Um, but you don’t want to get into a relationship where, “Oh, I thought you were going to write the specification. No, I thought you were going to write the specification. I thought you were going to help us narrow down that range.” Or, “I thought you were going to do that test method. Oh, I thought you were going to hand over that test method to us.” So those clear defined requirements from each side is super important very, very early on.

And you do [00:26:00] want to choose a partner that can go the distance with you, maybe even in different stages. So maybe you find a small CDMO that can take you through Phase One / Phase Two, but you’re going to have to look for somebody for your Phase Three and GMP manufacturing on a very large scale. But, um, all of these questions are very important and understanding capabilities is very important. And understanding your own capabilities, like what are you capable of doing in-house and what needs to be absolutely outsourced to other people?

Mike Kent: And I feel like being brutally objective in that process, um, is incredibly important because we can sometimes make assumptions that either we do have capabilities as the sponsor or that we might have capabilities as the sponsor or even that we don’t and we actually do. So being very objective in that process.

Just real [00:27:00] quickly to back up for those who may be listening that may not be as familiar with CMC. Can you talk about what CMC is?

Kim Lim: Yeah, sure. So, CMC is traditionally “Chemistry, Manufacturing & Controls”. This is a department that really takes your process from development into a proceduralized manner.

So things like, let’s talk about small molecule for a minute. So Development would come up with the molecule. CMC now comes up with the process of how to make that molecule, and make it reproducible and repeatable. So, that’s kind of what their role is. And then they hand it over to a full-scale manufacturing area where they would do mass production of what the process is. So they’re an essential part within the pharmaceutical environment where they’re the [00:28:00] gatekeeper right from the development into marketable material. So making that robust process.

An equivalent in medical devices is really your Engineering group. So, those people who initially help with the design of a medical device, but then you need a manufacturing engineer, industrial engineer to come in to look at the process of how it’s made, all the components, and then moving that into a full scale manufacturing process.

So, um, the, they’re really the, the technical group that, that brings it all together to create the manufacturing process that you would use going forward.

Mike Kent: Okay. To our earlier points in the discussion, that sounds like a mini internal tech transfer, right, going from Development or Discovery into this group that’s going to say, “Okay, thanks very much. We’ll [00:29:00] take it from here.”

Now, I think it’s also important to point out that you’re not talking about the Development group going away. They’re still involved in that process, obviously, as we go through and guiding that process. And that’s going to be a central theme to what we talk about in every tech transfer. You have that subject matter expertise that’s maintained through the process of whatever that next step is going forward.

To this point in our discussion with Kim, we’ve focused on how sponsor companies should begin preparing for tech transfer early on.

First, outline your Development Life Cycle, clarifying who should be involved, roles and responsibilities, process steps, key stage gates, and other decision points as they’ve been defined and agreed to up to this point. Now, this can and will change over time, so make sure the framework is updated as your [00:30:00] development process continues to mature.

Kim noted that Quality by Design as described in ICH Q12 is becoming much more of a regulatory expectation than just a suggested best practice for development activities. We’ll list ICH Q12 along with some other tech transfer resources for you in In the show notes.

 And Kim strongly encourages engaging contract partners way earlier than you think, including having them be a formal part of your Development team. Selection should be about more than their ability to pass an audit or having some basic technical capabilities. Things like communication, transparency, the level and quality of their collaboration and their ability and willingness to be in it for the long haul are all key determinants for success.

To work with Kim on your next tech transfer or validation [00:31:00] project, reach out to us by sending an email to connect at medvocon.com

Part Two of our Tech Transfer series with Kim continues the focus on sponsor partner collaboration and how contract organizations can set themselves apart, not just from a technical standpoint, but as a key partner that can actually accelerate the development process and improve the science.

We hope you’ll join us for that and more next time here on The Grind.

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 [00:32:00] website at http://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 http://www.medvacon.com.