Sept. 1, 2021

Pharma 4.0

Pharma 4.0

Augmented reveals the stories behind the new era of industrial operations, where technology will restore the agility of frontline workers. 

In episode 31 of the podcast, the topic is: Pharma 4.0. Our guest is Michelle Vuolo, Quality Practice Lead, Tulip.

In this conversation, we talk about GxP, the collection of quality guidelines and regulations created to ensure that bio/pharmaceutical products are safe, meet their intended use, and adhere to quality processes during manufacturing, control, storage, and distribution, specifically in the context of emerging digital technologies that promise to improve efficiency, so-called industry 4.0 or, in this case, pharma 4.0 technologies.

Augmented is a podcast for industry leaders and operators, hosted by futurist Trond Arne Undheim (@trondau), presented by, the frontline operations platform, and associated with, the industrial upskilling community launched at the World Economic Forum. Each episode dives deep into a contemporary topic of concern across the industry and airs at 9 am US Eastern Time every Wednesday. Augmented--the industry 4.0 podcast--industrial conversations that matter.

After listening to this episode, check out:

Trond's takeaway: Pharma 4.0 has to be executed with a diligence unseen in the software industry, which also explains why change has taken a while to come to pass. Now that the industry is taking on board the promise of such technologies, it also has to document its effects. The impact on digital technologies should be positive although it will not be without frustrations for those who want quick wins.

Thanks for listening. If you liked the show, subscribe at or in your preferred podcast player, and rate us with five stars. If you liked this episode, you might also like episode 33, Sustainable Manufacturing at Scale, episode 23, Digital Manufacturing in the Cloud, or episode 17, Smart Manufacturing for All

Augmented--industrial conversations that matter.



#31 Michelle Voulo_please edit

[00:00:00] Trond Arne Undheim, host: Augmented reveals to stories behind a new era of industrial operations where technology will restore the agility of frontline workers. In episode 30, one of the podcast, the topic is pharma 4.0, our guest is Michelle Voulo. Quality practice lead at Tulip.In this conversation, we talk about GXP, the collection of quality guidelines and regulations created to ensure that biopharmaceutical products are safe, meet their intended use and ear to quality processes during manufacturing control, storage and distribution, specifically in the context, so the merging digital technologies that promise to improve efficiency industry 4.0 or in this case, pharma 4.o. Technologies. Augmented the podcast for industry leaders and operators hosted by futurists Trond Arne Undheim presented by the frontline operations platform and [00:01:00] associated with MFG the industrial upskilling community launched World Economic Forum. Each episode dives deep into a contemporary topic of concern across the industry and airs at 9:00 AM us Eastern time. Every Wednesday, Augmented the industry 4.0 podcast, industrial conversations that matter. So Michelle, it's great to speak with you.

[00:01:27] I was curious, what is this animal called? Pharma? 4.0, yeah. 

[00:01:33] Michelle Vuolo: Yeah pharma 4.0 is really just taking at the top of the industry 4.0, which defines basically that we're in the fourth industrial revolution. The fourth industrial revolution is characterized by a lot of things, but. Mainly internet of things, type technology, the interconnected hyper-connected environments that we're in pharma 4.0 is really just taken that space.

[00:01:55] And some of those, the operating models around that and applied some guy [00:02:00] posts in particular, the guy posted like ICH Q nine guidelines to put it into the perspective of pharmaceutical quality systems. And they've come up with an operating room. 

[00:02:09] Trond Arne Undheim, host: And you have been deeply involved with this? Certainly before you came to tell me about this ISPE group in pharma, what kind of association is that and what exactly is it that they're, that you have put in place?

[00:02:22] Yeah, sure. 

[00:02:23] Michelle Vuolo: So I S P E is the international society, pharmaceutical engineering I would say that they're most known for in the world in a lot of cases for the gap, a good automated manufacturing practices, guidelines that the industry knows and loves for validating computerized systems.

[00:02:40] So they're the authors of Gant number one, but they do a lot of other things for pharmaceutical. And so they also are, have basically trademarked pharma 4.0. And so they are industry leaders on the topic. And like I said, they developed an operating model around pharma four point. Oh, 

[00:02:58] Trond Arne Undheim, host: How did you get involved with [00:03:00] quality assurance in pharma, it's a pretty specific field. It's important, but it's not something everybody I meet an expert in. 

[00:03:10] Michelle Vuolo: Yeah. And I certainly didn't go to school to be a quality professional. I happened upon it like a lot of people do. I started my career in QC doing so the bench chemistry testing for a pharmaceutical product, and then moved my way into CRA quality operations and supported product lines and products products release and things like that.

[00:03:32] You ultimately got into it, the roles within the pharmaceutical world before jumping over to tools. But I've been in, I've been involved in ISPE through most of my career. Just a lot of it was more tangental, but now it's obviously in a much more active role. 

[00:03:47] Trond Arne Undheim, host: So I understand that pharma four is very tied to the industry 4.0, but good practice and good sort of, I believe you call it GXP in the pharma industry.

[00:03:58] It is clearly [00:04:00] also, or has been more than that. What is this movement for around pharma moment for quality around farm. I, it doesn't have to do with safety oh, clinical trials, or is this specific to other type of processes around the industry? 

[00:04:14] Michelle Vuolo: Yeah. So GXP is really a catch all term for all regulations.

[00:04:19] There's G CP for clinical practices. There's the MP for. Manufacturing practices there G there's GPB for a good pharmaceutical. I'm sorry. Pharmaco vigilance practices. So GXP really encompasses all, basically all regulations around pharmaceutical and even med medical devices, basically life science products in the industry.

[00:04:41] Trond Arne Undheim, host: And where are we now with these with these regulations? To what extent. Has a pharma started to take on board industry and pharma 4.0 and how early are we in the adoption process? 

[00:04:56] Michelle Vuolo: Good question. I would say we are, there's a whole [00:05:00] continuum, right? There's a lot, there's some companies that are very much stuck in, I would say like pharma one, footnote two, our 2.0 3.0.

[00:05:08] Back in more manual processes. Or even some have started to computerize their processes, like more in a paper on glass type situation. But definitely not pharma 4.0, which is really taking account for digital artifacts, but also there's a whole other component that has not been embraced fully, which is like the workforce of the future, which is part of that, the culture piece, the democratization, there's so many aspects to farm a 4.0 to really fully realize the benefits.

[00:05:39] Trond Arne Undheim, host: Tell me how a software firm or, what started out, as a software company can interact in, in this fair. Cause I imagine that there's a, like you pointed out there, there are all these different. Stages of getting involved with this technology. So how does software firms play in this space with pharmas, which [00:06:00] historically were pretty separate firms.

[00:06:02] I guess they were worked working with outsourcing companies, but for very specific kind of parts of their clinical trial stages. How does this kind of new technology element enter into it? 

[00:06:15] Michelle Vuolo: Yeah first and foremost Digital companies can really start working with life science companies by, I think there's some baseline features and functionality that they need to comply with.

[00:06:26] It just a few that could just come to mind are like electronic signatures. For example data integrity is also hot buzz. I would be amiss if I had a conversation about this and to not bring up data integrity all these aspects around that. Because data, especially in the pharma 4.0 world is so very important, become central to everything.

[00:06:43] But features around supporting those types of things, access controls, all these things that are very near and dear to achieving integrity of our data to come up and have those types of features 

[00:06:53] Trond Arne Undheim, host: So there surely then is a bit of a path also for a young firm that wants to work with with any regulated [00:07:00] industry.

[00:07:00] But very specifically with pharma, tell us about To what extent the industry is embracing this kind of contact and how fast it is moving into being able to contract with, these emerging firms that are, they will keep emerging and they will, all of them have this learning journey before they can comply the way that the industry needs it to do.

[00:07:22] Michelle Vuolo: Sure of course, there's like a barrier to entry of course. And a lot of that is, is imparted in knowledge and understanding of the needs. You can meet the baseline requirements, but then you can also, achieve the essence of what they're trying to achieve. And I think with more maturity and knowledge of these companies to be able to understand these things.

[00:07:40] Is really gonna differentiate an emerging technology supplier from a supplier that can really meet that the needs of of the regulated customers. Also, there is supporting documentation and support that that pharmaceutical companies need in order to I would say, take on and deploy [00:08:00] new technologies quicker and easier. It's also building a trust, a trustworthy relationship between the two companies and, having quality management systems and providing that sort of level of of Compliance 

[00:08:13] Trond Arne Undheim, host: Briefly. What is the future?

[00:08:15] What does the future hold for pharma 4.0? Is it something that we're going to be seeing throughout this decade? Or is it a process that kind of, once it gets going more or less, the entire industry will start to adopt many of these principles in a fairly rapidly. What do you see happening?

[00:08:36] Michelle Vuolo: Like data integrity, a topic that's been around forever and essentially a topic that's not new, but just put a tag word to it. Pharma 4.0 is a tag word, but it is really characterizing a whole bunch of things. One of them is digital maturity. Okay. That is a main piece to pharma four point.

[00:08:52] No, but it's not the only thing. We've talked about. Resources and the workforce of the future, really enabling our [00:09:00] people to to be knowledgeable about the areas that they're that they're managing and handling also the democratization and then the less hierarchical structures.

[00:09:08] There's a lot of things that need to be embraced. I think right now because of what's happened in the last year or so I think the industry is getting more primed to take on change any evolve and dive into an evolution that's only quickening. I think the time is right.

[00:09:24] And it is happening now. I don't think it's a short-term thing. I do think that this is something that's going to be evolving over a long time. We have things that are happening in our personal lives, in our home lives that go beyond by far what we're doing in the pharmaceutical world with like machine learning and artificial intelligence and all these really cool things that are happening in our homes.

[00:09:45] And, with our smart assistants and all these things that we haven't. Started to embark on in the pharmaceutical world to any depth. So again, I think there so many levels of maturity here that if this is going to be around for awhile and [00:10:00] there going to be pieces of it, that companies are going to be more.

[00:10:03] Willing to bite into. But I think that's only going to pick up over time to be honest with you. But there are a lot of things that we need to do and not just buy cool new technologies, but we have to work with our people and recognize that our workers are frontline. They're always going to be frontline and we need to provide them resources to further develop themselves, and really take care of.

[00:10:24] Credit for that resource. 

[00:10:28] Trond Arne Undheim, host: You are a bit of a crossover. What are some of the surprises that you have had as you've moved on to the newer kind of younger firms but still working, in the general space of of quality. What were some of the surprises that you've had working with Tulip specifically? 

[00:10:46] Michelle Vuolo: 

[00:10:46] It's funny by crossover. I assume you mean 

[00:10:48] Trond Arne Undheim, host: so will you straddle kind of the pharma world and the software world is what I mean? Yeah. 

[00:10:54] Michelle Vuolo: So now I jumped over into the software world. Yeah, I did. And I did that on [00:11:00] purpose. It was a really exciting area because so many cool things are happening right now, but I wouldn't have just done it just to do it.

[00:11:06] I'm doing it also because I do am, like you said, straddled with the life sciences. I really want life sciences to get to a place where they can I don't know take on these technical tools, these new digital tools and take these things on quicker and faster and evolve better, ultimately achieving faster life cycles of our products and, with personalized medicine and some of the other things that are happening out there, we need to be able to evolve fast.

[00:11:32] I felt by jumping over to the other side, that I could be more effective in trying to help the industry in that way. By surprises, really nothing, but I, I feel like I jumped over for a reason and I'm realizing that reason, the fast evolving scenario that is in technology is so very exciting that I I really want life sciences to be able to embrace that.

[00:11:54] Trond Arne Undheim, host: So again, if you're thinking about the future, do you foresee a time when that pharma [00:12:00] companies themselves will, again, try to take on all of these technology tasks? Or do you think that the way that with the pharma 4.0 principles that. We're going to be able to find this more seamless and standardized way to interact between companies so that it actually is sometimes faster to just contract or work with partners because truly the process has been ironed out and all of these new technologies can be available, but you still have the quality and the predictability of the process of the past.

[00:12:33] Michelle Vuolo: Sure. Yeah, absolutely. I think the ultimate goal is to get to this. Seamless Nirvana of like ease of, capturing and bringing in new technology so that we can evolve fast and quick. Now, of course, I've lived long enough in the life sciences industry to know that, there are reasons why it's not today, right?

[00:12:52] Like we do have to demonstrate control, this word term, this term called validation that, seems to slow things down or the perceived [00:13:00] slow things down. Yes, we are working towards ways to try to make that validation or the demonstration of control, be more seamless, right? In ways that, trying to shift our focus towards data centric approaches and things like that.

[00:13:14] And really to focus on mitigating risks at the data level, to be able to demonstrate that control and not be so wrapped up in the individual components along the way is really trying to get us to a, something that is more seamless and get us to that area and that, get us to that.

[00:13:33] Like I said, that Nirvana, that way, that's that area where we can bring in new technologies quicker and faster 

[00:13:39] Trond Arne Undheim, host: and a validation for Pharma 4.0 very specifically that's another on top of of the pharma term, it's just specifically focusing on validation. What are the 4.0 aspects of validation, but what changes with the technology aspect for it, for the validation practice that, that companies in the pharma space I used to.[00:14:00] 

[00:14:00] Michelle Vuolo: Yeah, so this is a fast evolving area right now from a, for us to say validation 4.0. Is this working group within pharma 4.0 where we're specifically looking at this topic of validation and the floor at 4.0 world. It, the, the premise and basis of it is quality by design aspects, which is an ICH guideline the premises about processing data now.

[00:14:23] But we are trying to overlay, process and data knowledge with data mapping and risk mitigation at that level, regardless of the digital tools that they're using. So this is really more of a holistic view of validation. It's also looking at utilizing all the data resources that we can, whether it's from design and development, whether it's from current pharmacovigilance, like post-market data.

[00:14:47] But bringing those data points into the manufacturing space. So we can look at continuous flow of data that's out there too also validate our risk levels and our [00:15:00] control levels. It's again, it's really, like I said, that the two main premises are quality by design and data from all aspects of the product life cycle.

[00:15:10] Trond Arne Undheim, host: If you see it from a user level, in an organization, a lot of what you guys come up with turns into. Compulsory courses and compliance requirements. What should one think, if I am taking a course that has been mandated by a quality process, what should be the mindset and how do you avoid that?

[00:15:29] All of this kind of training and preparation becomes more than a course, because I my guess is that the Nirvana we're talking about here is one where you're only doing these courses to verify that the process already is working well. You're assuming that the process. Has already changed so that the verification through sort of courses and making sure that everyone knows what's going on is almost like an after.

[00:15:57] I thought it's more, just a [00:16:00] double-check how, but it doesn't always feel right like that. I guess if you're trying to get up this very steep learning curve and feel that there are a lot of requirements and things that you need to take into account, what is your advice to employees? Either on the pharma side or on the it side that are trying to.

[00:16:15] I guess upskill themselves very quickly to get to the level that they can be contributors and certainly not to the detriment of company contracts, following all the right procedures and you're not doing things right. 

[00:16:28] Yeah. 

[00:16:29] Michelle Vuolo: I just thought one first point I would highlight is Requirements as in regulatory requirements, don't change very often, right?

[00:16:38] The point is that the interpretation and the implementation approach is what evolves right with given with, not the way of the wind, the new hot topic or whatever, like data integrity has been very hot for awhile from, pharma 4.0 is now a new tagline. I think again, The ultimate is going to be process [00:17:00] understanding, but what is emerging more important to that is data data management, data flows, data the importance of data, right?

[00:17:08] So the more to the extent that we can understand our data flows and what the not the implement implications, but the interactions of between data points is really becoming the most important. So to the extent that we can understand our data flows, understand what data points are critical to control over and above the process.

[00:17:27] That is the most important, I've been hearing data scientists and things like that are definitely, the thing of the future, I would agree with that. We have to understand our data, data integrity was almost like a precursor to this. Like we know we have to have integral data.

[00:17:40] Now we need to understand our data flows and control them. And to the extent that we can do that and focus on that, not that I'm not saying it's a black box type validation approach, but I'm just saying that. Controlling our data, regardless, like system agnostic equipment agnostic is the focal point here.[00:18:00] 

[00:18:00] And bringing in data points that sometimes may not have shown cause and effect are becoming more important to us. Like I said, I was bringing in data from design and development through the manufacturing process, but also pharmacovigilance and real-world data. It really needs to be brought into the manufacturing space also to demonstrate interaction.

[00:18:22] Trond Arne Undheim, host: So here's the question for you? I very much want to learn pharma 4.0. This is actually even true. It's not just the question. Where do I go? 

[00:18:31] Michelle Vuolo: Yeah. Yeah. Like I said, you can just search it up on the internet. But I think so the folks that are writing a lot about it are ISPE I would say that there's not really.

[00:18:42] Hard guidance is out there right now, but there are many articles that have been put out by it iSPE in pharmaceutical engineering magazine that not only lay the foundation for the operating model, there's been some maturity model articles that have been written. [00:19:00] That's most, that to me is one of the main areas.

[00:19:03] But there's a lot out there. And, I think a lot of people are starting to tag to that name just because it's people are starting to understand what it means. It's still, in my opinion, when talking to some people it's very much this theoretical topic to a lot of people. And so this is what I like about the ISP model is it's broken down into we talked already about the information systems or the D obviously we know digital maturity is a piece, but the resources and workforce of the future, people have been talking about workforce 4.0 or workforce that future all the same topic. We need to figure out what these people need to be doing, going through organization and processes need to change and evolve in culture. Culture is this piece where, I think we're using the hierarchal nature of decades past where democratization and really letting our subject matter experts start driving the truck a little bit more is, is another big piece to it.[00:20:00] 

[00:20:00] So there's many different aspects to this that Need to be addressed. And, again, they, you can read up on the on the operating model, but there are several different topics that lead all into this sort of environment 

[00:20:11] Trond Arne Undheim, host: has the industry lastly, done any research on what the forecasting, I guess the impact of implementing this fully?

[00:20:21] What are the impacts potentially of implementing. At any kind of a 4.0 program inside of a pharmaceutical company? Are there efficiencies or is it more on the quality and assurance side? W what exact tangible benefits are, is one expecting from this? Not just, in regulatory in, on the regulatory side, but more on an, a, on a process side, or if you are a leader in the industry what would be your main objective and and goal.

[00:20:47] And then reasoning for entertaining, such a for bringing in this kind of perspective really fast or significantly into your organization. 

[00:20:55] Michelle Vuolo: Yeah. I think it's all those things, and of course I would say that. But yeah it's [00:21:00] efficiencies. It's, I think it continuous verification, continuous validation.

[00:21:04] So we don't have to do these like validation activities that are snapshots in time, but we're always doing it by, by bringing in these these new data points, but at the highest levels of if you read up on the pharma 4.0 Maturity model. The ultimate level of maturity is having completely autonomous change management, right? So you get to predictive capabilities and then you have an autonomous type capability. So at the predictive capability level, you have systems and data telling you that this is going to happen. And so you can make a change and you do it before before an issue or risk occurs.

[00:21:40] But in the highest level you have a self autonomous changing machine that. Identifies an issue and makes its course correct by itself. That's, that is the idea is that, we can do that before realizing risk or harm or anything to our products or patients, 

[00:21:57] Trond Arne Undheim, host: that brings me, to the really futuristic [00:22:00] question is, w what role, if any, can AI have, isolated from people in this very sensitive space, because eventually these are turning into clinical decisions or they're effecting clinical decisions. Is that also part of the framework to start safeguarding both kind of on the ethical side and on and putting in place processes that would stop runaway algorithms that are starting to act in strange patterns or something like that.

[00:22:27] Is that also eventually, do you think part of this a 4.0 landscape? 

[00:22:31] Michelle Vuolo: Yeah, absolutely. It is. It's in this is a topic that goes across several different things. 4.0 is looking at that and some case studies and models. Also there's a gap working group within ISP that has a specific group looking at AI and machine learning, artificial intelligence and machine learning.

[00:22:50] There are case studies that we're looking at in that space as well, from a validation perspective cause then the topics. Can we look at this as a black box? What, what really do we need to, be able to do [00:23:00] yeah. W these are all topics that we're definitely looking at.

[00:23:02] Obviously with the ultimate goal of protecting our patients, for sure. That's always the goal. But yeah, if we are to rely upon these technologies to start making some decisions we still have to demonstrate control. How do we do that? 

[00:23:16] Trond Arne Undheim, host: Yeah it certainly seems to me, it's a very fertile area of manufacturing, right?

[00:23:21] Things are really moving. And like you pointed out the last year has presented us with some challenges that have motivated pretty much everybody in the industry. And then everyone watching suddenly started watching more carefully. What this industry is doing. So it must be a bit of a victory lap in, in that sense to see so many progress points over the last few months and weeks in this industry, how do you feel like the industry is, dealing with this a success, are they resting on their laurels?

[00:23:51] So do you feel like this actually truly motivates to further rapid change? Because it has very rapid. And at least, from the outside, you would [00:24:00] hope that those are true changes, but to what extent were they actually not embedded in a quality process? They were like emergency use authorizations.

[00:24:10] When relaxed, we'll because that's the discussion in other parts of the medical system, right? I was just speaking to a tele-health expert and, he's pointing out that once these emergency regulations labs, unless we put in place certain safeguards, you risk losing some of the progress just because not just the momentum is lost, The legal room to act would perhaps also be lost.

[00:24:34] There are a lot of people thinking, we have made all this massive progress. 

[00:24:37] Michelle Vuolo: It's a good question. And honestly, I think only time will tell I personally and trying to capitalize on this momentum a little bit, while people are primed and open right now's the time to pounce, so to speak, right?

[00:24:50] If people are, then we've got to continue to show them and continue to push. I think that's the only way. We are creatures of habit. We've been doing this for decades year, [00:25:00] whatever it might be. Yeah it's too easy to fall back into old ways. Yeah, I, my hope is that people who are out there driving this industry can continue to push and drive forward while people are primed and open and ready.

[00:25:12] I think there's been many examples of where. It's been successful. It's been fine. What have been the re by going through some of these emergency processes the risk benefit was there so we went forward with it. And there, I think we've shown success in some of these areas.

[00:25:29] So my hope is that we capitalize and continue to drive forward with this moment. It's a time we are responsible to continue forward right now, yeah. 

[00:25:38] Trond Arne Undheim, host: Thanks so much, Michelle. It was great to chat with you about these important issues in pharma 4.0, 

[00:25:46] Michelle Vuolo: thanks. 

[00:25:48] Trond Arne Undheim, host: You have just listened to episode 30, one of the Augmented podcast with hosts Trond Arne Undheim , the topic was pharma 4.0.

[00:25:56] Our guest was Michelle Voulo quality practice lead [00:26:00] at Tulip, we talked about how to implement industry 4.0 technologies in such a regulated space, such as the pharma industry. My takeaway is that pharma 4.0 has to be executed where they diligence unseen in the software industry, which also explains why change has taken a while to come to pass.

[00:26:21] Now that the industry is taken on board, the promise of such technologies, it also has to done it's effect the impact on digital technologies. It should be positive, although it will not be without frustrations for those who want to quit. Thanks for listening. If you liked the show, subscribe at Augmented or in your preferred podcast player and rate us with five stars.

[00:26:46] If you liked this episode, you might also like episode 33 sustainable manufacturing at scale episode 23, digital manufacturing in the cloud or episode 17 smart manufacturing. We're all [00:27:00] Augmented industrial conversations. That's matter.


Michelle Vuolo

Quality Practice Lead at Tulip

Michelle currently leads the Quality Practice at Tulip Interfaces, Inc, who develops and sells a frontline operations platform where manufacturers of many industries can build digital content to manage their operations. Before joining Tulip Michelle spent over 24 years in the biopharmaceutical and medical device industries in many different roles ranging from QC laboratory, engineering technical support, Quality Assurance management and Computerized Systems Compliance. Michelle has a strong understanding of the needs of the life sciences industry and is now motivated and driven to evolve stagnant ways of meeting compliance requirements, especially as it relates to the 4.0 world. "My main mission is to stay current in our ever changing world. Staying current means to be outwardly active, remain open to evolution, and seek efficient, effective means to meeting needs in new ways.”