1 00:00:01,590 --> 00:00:06,000 So could you just start by saying your name and your job title and where you where you work? 2 00:00:06,840 --> 00:00:11,200 Yeah, I like my name is Katrina. So my job, Petroleum Institute, 3 00:00:11,430 --> 00:00:23,340 I work as a senior research scientist on my project is mainly develop a process for large scale manufacturing in the GMP laboratory for human use. 4 00:00:23,610 --> 00:00:32,520 Yeah. So can you tell me how you first got interested in science and what the main sort of steps in your career were until you came here to Oxford? 5 00:00:33,360 --> 00:00:37,720 Yes. I spend fairly old stories like I. 6 00:00:38,750 --> 00:00:46,620 I was always gravitating towards science rather than social science since my primary junior in high school. 7 00:00:46,620 --> 00:00:49,650 And then. And where did you grow up? Tell me where you grew up. 8 00:00:49,890 --> 00:00:53,070 I grew up in Indonesia. In Jakarta? Yeah. 9 00:00:53,170 --> 00:00:57,270 Like I'm a long way. Mm hmm. So, yeah, I. 10 00:00:57,480 --> 00:01:01,770 Since I was little, I was always like science. Yeah. 11 00:01:02,010 --> 00:01:05,370 I mean, a lot of it is quite fascinating to me. 12 00:01:05,370 --> 00:01:08,790 Like, uh, physics, biology, chemistry. 13 00:01:09,270 --> 00:01:13,530 It's more interesting to me than business or history. 14 00:01:14,220 --> 00:01:22,680 And, and then I don't really know what to do until I was actually in the last semester of high school. 15 00:01:23,190 --> 00:01:27,870 So my parents always wanted me to be either an engineer or a medical doctor. 16 00:01:28,740 --> 00:01:35,129 So I was thinking maybe I, I would be one of them, think it'd be an Indian or a doctor. 17 00:01:35,130 --> 00:01:49,140 But in the last semester of my high school, my biology biology teacher was having a presentation about this new science field called Biotechnology. 18 00:01:50,400 --> 00:01:55,140 And it's been a topic during my time, 19 00:01:56,010 --> 00:02:04,740 and I think the topic is what molecular biology is changing the genetic of fish from monochromatic like black and white into some colourful fish. 20 00:02:05,400 --> 00:02:09,570 And then I was really in the seventies, had never seen like it before. 21 00:02:09,570 --> 00:02:17,070 So I read about it more and then I got interested in this biotechnology field. 22 00:02:17,610 --> 00:02:22,730 So the idea that you could manipulate the genes of an organism to make it something different and that's right. 23 00:02:22,980 --> 00:02:35,100 So I could actually change the penalty of organism, life changing the DNA of that organism, and then it will be shown up to the manipulation. 24 00:02:35,890 --> 00:02:43,500 Yeah, it's quite fascinating. This this what makes me decided to study science during my college. 25 00:02:44,280 --> 00:02:47,740 And what course did you do at college? I did biotechnology. 26 00:02:47,760 --> 00:02:52,110 Oh, yes. So they had a course that did exactly what you wanted. 27 00:02:52,480 --> 00:02:59,220 Yeah, that's right. Yes. And and what did you what kinds of research. 28 00:02:59,640 --> 00:03:02,760 So did you do any research work as part of your undergraduate? 29 00:03:02,950 --> 00:03:11,010 Yes, that's part of my undergraduate. We did some kind of a research project, but it's not really delves deeply into the science. 30 00:03:11,340 --> 00:03:16,950 It's mostly like doing what the supervisor told you to do. 31 00:03:17,080 --> 00:03:20,820 Yes. Yes. So I guess not the experiment, superficial experiment then. 32 00:03:20,850 --> 00:03:25,000 And then you write the lab report. So I get into deeper science. 33 00:03:25,010 --> 00:03:31,470 So I actually I started my master in biotechnology is still master by coursework, 34 00:03:31,950 --> 00:03:37,380 but I spend most of my time working in government laboratories in Australia. 35 00:03:37,560 --> 00:03:43,049 Oh right. So you that you travelled to Australia for that. Certainly a to do list of course. 36 00:03:43,050 --> 00:03:47,490 Which, which university. Royal Melbourne Institute of Technology, RMIT. 37 00:03:47,820 --> 00:03:50,980 Mm hmm. And what was the topic of your most? 38 00:03:51,000 --> 00:03:56,819 Is it still master by coursework? But it's master of biotechnology. 39 00:03:56,820 --> 00:04:01,950 So we learn a lot, theoretically and practically in the laboratory. 40 00:04:02,670 --> 00:04:08,880 But yeah, I did full time master, but in during my first semester of my master, 41 00:04:10,890 --> 00:04:16,890 the lecturer offer me a position of internship in this governmental government 42 00:04:16,980 --> 00:04:22,350 lab called CSIRO Commonwealth Scientific Industrial Research Organisation. 43 00:04:23,040 --> 00:04:27,120 And I spend most of my time working full time as an intern there. 44 00:04:27,450 --> 00:04:30,960 So you did a full time course and a full time. Yes. Yes. 45 00:04:31,410 --> 00:04:38,010 So the master of lifestyle actually designed to to me partake. 46 00:04:38,220 --> 00:04:41,570 When you're fully employed. I see. 47 00:04:41,580 --> 00:04:54,059 So most of the coursework was done at the later time around 6 p.m. onwards and most of the lab courses is in a weekend or in the full time, 48 00:04:54,060 --> 00:04:59,970 like two weeks intensive, full time laboratory timetable. 49 00:05:00,570 --> 00:05:04,850 I'm so sorry. Keep you going. 50 00:05:04,930 --> 00:05:08,190 It's just I was able to do both. 51 00:05:08,370 --> 00:05:12,750 I mean, it's quite hectic. What? I couldn't. I couldn't do my work and my. 52 00:05:13,110 --> 00:05:26,970 My study at the same time. And then, yeah, after that, my boss in in that CSIRO lab offered me a new position. 53 00:05:27,270 --> 00:05:30,720 Was still connected to the university. Mm hmm. 54 00:05:31,200 --> 00:05:37,410 And then, yeah, I started to take some research project which related to the vaccines. 55 00:05:37,980 --> 00:05:43,110 Let's see. We started on vaccines at that point. And what what kind of vaccines were you looking at then? 56 00:05:43,320 --> 00:05:53,070 So as a base of my research topic, we were employing a technology called the virus like particle. 57 00:05:53,220 --> 00:05:57,780 Mm hmm. So at the time, I use hepatitis B fast like particle. 58 00:05:58,200 --> 00:06:02,820 And so I used one of the protein called surplus antigen. 59 00:06:03,540 --> 00:06:07,110 This is most of us antigen to make a stronger hepatitis B vaccine. 60 00:06:07,530 --> 00:06:14,970 And I also use the technology to design cancer targeting vaccines. 61 00:06:15,090 --> 00:06:22,650 Mm hmm. Yeah. So overall, during your time, both really from your undergraduate all the way through your graduate work in Australia, 62 00:06:23,040 --> 00:06:29,400 you were getting a really thorough technical training in how to make vaccines, in how to make vaccine. 63 00:06:29,410 --> 00:06:37,740 Yes, that is for my research project and the time I also working at the same time working full time in the governmental laboratory, 64 00:06:38,550 --> 00:06:41,580 uh, dealing with mostly manufacturing, 65 00:06:41,580 --> 00:06:47,430 which is the work that I'm doing now, which is a large scale manufacturing for drugs and vaccines, 66 00:06:47,970 --> 00:06:55,410 which after this up to the standard that humans can use, which is called good manufacturing practices. 67 00:06:55,540 --> 00:06:57,400 Yeah, that's right. Yes, yes, yes. Yeah. 68 00:06:58,200 --> 00:07:07,380 And so that well, that again, really meant that you spent a lot of time at the bench, presumably physically doing the work that was involved. 69 00:07:07,740 --> 00:07:14,490 Um, I suppose this is quite a good time to ask you. Um, can you just explain for the benefit of people who don't know. 70 00:07:17,150 --> 00:07:19,459 In a reasonably short space. 71 00:07:19,460 --> 00:07:30,050 How do you get from identifying a pathogen like a virus to having a vaccine in millions of vials ready to inject into a population? 72 00:07:30,440 --> 00:07:33,770 What are the key steps you have to go through to get there? 73 00:07:34,160 --> 00:07:41,060 Okay. So yeah, first, once we noticed this like a new pathogen and we would like to identify it. 74 00:07:41,180 --> 00:07:44,570 And usually we do like whole genomic sequencing. 75 00:07:45,170 --> 00:07:58,700 So we find we extract the DNA from the pathogen and we treat what is in their DNA and then it and from that certain DNA. 76 00:07:58,700 --> 00:08:03,169 And then a second part of that DNA, which is quite immunogenic, 77 00:08:03,170 --> 00:08:14,060 the means it will induce your immune response when it's maybe when the pathogen is inside our body. 78 00:08:14,180 --> 00:08:18,440 So a certain bit of the pathogen will induce quite a strong immune response, 79 00:08:18,770 --> 00:08:30,350 but certain immune response is not really neutralising, then it wouldn't help you fighting off the virus. 80 00:08:30,380 --> 00:08:38,570 So we have to identify which part of that pathogen which actually benefit us in inducing the enormous immune response to protect us. 81 00:08:39,650 --> 00:08:44,720 That's what this what the part of the pathogen that we are interested in. 82 00:08:44,930 --> 00:08:53,840 Mm hmm. So after we could identify that, and then now we know the reading of the sequence of the DNA, 83 00:08:54,380 --> 00:09:03,290 we could take that sequence and then use there many different vaccine technologies. 84 00:09:03,560 --> 00:09:08,780 And there are some are named Firefly Viral Vector. 85 00:09:08,900 --> 00:09:13,110 There are DNA vaccines or they are proteins, vaccine or subunit vaccines. 86 00:09:14,450 --> 00:09:23,300 But essentially, you want to find a way of delivering something that is not itself going to make people ill but will provoke the immune response. 87 00:09:23,430 --> 00:09:25,999 Yeah, after we identify a bit of the pathogen, 88 00:09:26,000 --> 00:09:36,379 we need to to have a vehicle to deliver that piece of genetic information to our body, we're not actually harming the body. 89 00:09:36,380 --> 00:09:46,520 So we would like to train our body with this part of the pathogen, I mean, still without harming the bodies. 90 00:09:47,000 --> 00:09:51,020 So with that, we employed different kind of vaccine technologies. 91 00:09:51,890 --> 00:10:00,560 And and then we, of course, we have to formulate the physical with that part of the pathogen inflammations. 92 00:10:01,280 --> 00:10:09,040 And then usually we do it in the lifecycle first, and that's what I'm thinking. 93 00:10:09,050 --> 00:10:18,790 So to begin with, you just need a, you know, a metre of bench space and a lot of luck in doing this and doing the recommendation. 94 00:10:18,890 --> 00:10:33,030 Yeah, because, you know, there's a lot of combination that may not work and you have to formulate it in the in in the fashion that I know the vaccine 95 00:10:33,060 --> 00:10:45,530 should be stable and and in the cleanest way possible that it will not bring any bacterium from the environment into your body. 96 00:10:45,960 --> 00:10:50,180 So we call it, um, low end toxin. 97 00:10:50,510 --> 00:10:59,930 Mm hmm. So there's a different standard between a lab scale and GMP manufacturing, uh, products. 98 00:11:00,590 --> 00:11:07,999 And that's not just about not increasing a stay on the scale, but it's about the quality of the product. 99 00:11:08,000 --> 00:11:11,480 So we call it. Yeah. 100 00:11:11,510 --> 00:11:18,980 I mean, the clinical lab yield good laboratory practice, a standard production, GMP product. 101 00:11:20,120 --> 00:11:32,240 So after you have your vaccine, you actually already produce it so far faster than you make your vector or a plasmid, 102 00:11:33,740 --> 00:11:38,690 which is just like a piece of little piece of DNA. DNA, and then put it inside the cell. 103 00:11:38,870 --> 00:11:46,700 The cell will make the virus, which is your vaccine for you, and then you can gradually will scale it up. 104 00:11:47,960 --> 00:11:52,100 So you need volumes of cells? 105 00:11:52,440 --> 00:12:09,650 Yep. But they're essentially working as little factories that are making the vaccine. 106 00:12:09,710 --> 00:12:14,460 Yeah, this. Yeah, these cells can be purchased commercially. 107 00:12:14,480 --> 00:12:19,010 I mean, they are widely available in the public. 108 00:12:19,310 --> 00:12:25,730 I mean, pharmaceutical companies and the Saudis working in a little factory, mimicking the bodies. 109 00:12:26,240 --> 00:12:39,320 But this is called help ourselves. So they actually contained a genetic sequence that will help fighters multiply, which our body doesn't have. 110 00:12:40,660 --> 00:12:50,239 So we put the virus in that sort of cell to help our cells, and the cells will make the virus or the vaccine for you. 111 00:12:50,240 --> 00:12:53,600 And then we have to separate the vaccines from the cells. 112 00:12:54,530 --> 00:13:01,490 It's just we call it the contaminant because the protein from the cells couldn't get into our body. 113 00:13:01,670 --> 00:13:07,880 Right? Yeah. You don't notice up until the laboratory scale. 114 00:14:10,300 --> 00:14:13,810 So. But there are also three stages of clinical trial. 115 00:14:15,400 --> 00:14:25,780 The first stage is to assess if the vaccines are actually safe in that small populations. 116 00:14:26,500 --> 00:14:33,340 But to start doing the clinical trial use, you have already have a product that can be used in human. 117 00:14:33,910 --> 00:14:41,410 Ms. Your vaccine has to be produced in the clinical are up to the GMP standard and you need quite a lot of it. 118 00:14:42,010 --> 00:14:50,559 Yeah, we need to love it. Yeah. So the scale of that, that's the point at which you have to start thinking about using bigger vessels. 119 00:14:50,560 --> 00:14:57,490 And I mean, is it simply just a matter of increasing the size of the vessel or are there other complications in going from 120 00:14:57,490 --> 00:15:02,979 what you can do in a lab to what you need in order to produce enough for a trial for the first clinical trial? 121 00:15:02,980 --> 00:15:06,720 I mean, the the scale will not be so different from the labs. 122 00:15:06,990 --> 00:15:14,610 All right. Yeah. Yeah. So if you it's only for a first clinical trial, you will give the vaccine to, like, ten or 20 people. 123 00:15:14,710 --> 00:15:18,820 Okay, then you only need a few teaspoons of vaccine. 124 00:15:18,880 --> 00:15:30,280 Yes, that's right. So the doses will not be hugely different from the bench skill, but you need to have a process that is aseptic, 125 00:15:30,550 --> 00:15:39,730 which is can be done in close environment with the cleanest possible equipment. 126 00:15:39,730 --> 00:15:51,760 And most of the time we use a single use technology in the GMP environment lab and then for the clinical phase two and three, 127 00:15:51,760 --> 00:15:58,959 which we assess, starting to assess their immune response and immunogenicity if it's working in the larger population. 128 00:15:58,960 --> 00:16:05,050 Plus if it's still is there any side effects in this larger population, 129 00:16:05,050 --> 00:16:12,700 we need to give them 200 or in the phase two and tens of thousand people in the pastry. 130 00:16:12,940 --> 00:16:18,040 Then we have to start scaling up to a larger scale. 131 00:16:19,150 --> 00:16:25,600 There's quite a complication in scaling up the process. 132 00:16:25,600 --> 00:16:41,230 Firstly, yeah, yeah. We need to think about the storage because some of the GMP facility doesn't have a large storage which include our GMP facility. 133 00:16:41,500 --> 00:16:52,930 It was designed for the clinical baseline. So there's not many big bioreactor that can be used there. 134 00:16:52,930 --> 00:16:59,260 I mean, I think they only use a single use shaker which can fit into the incubator. 135 00:16:59,800 --> 00:17:11,050 Other than that, we need to think about, yeah, the the flow, the flow of the process. 136 00:17:11,620 --> 00:17:19,750 So in the GMP facility, we have to, uh, we need to separate between the waste and the product. 137 00:17:21,580 --> 00:17:33,430 So, uh, and some completion is mostly what the calculations, what is the flow of the, what is the flow of the input from the upstream. 138 00:17:33,670 --> 00:17:39,610 And there are many jargon. Yes, and that's, that's essentially an engineering problem. 139 00:17:39,610 --> 00:17:46,420 Yeah. This in engineering. So you really combined your two original interests, the biotechnology and the end or the medicine or the engineering. 140 00:17:46,720 --> 00:17:51,930 You're talking about creating vaccines, and that's very much a biological piece of work. 141 00:17:51,960 --> 00:17:57,040 Once you get to this stage of needing to get the manufacturing process going. 142 00:17:57,400 --> 00:18:00,560 It is. It is. It's an engineering problem. Yeah. 143 00:18:00,790 --> 00:18:03,339 I mean, there's a lot of room for in the upstream, 144 00:18:03,340 --> 00:18:14,530 which is the term that you use in the beginning of the process of how you make the lots of virus inside the cell. 145 00:18:15,060 --> 00:18:22,630 We call it an upstream process if you're only making it in the small amount so you don't have to think of the strain limits, 146 00:18:23,080 --> 00:18:28,180 the scaling up from a small volume into a large bioreactor. 147 00:18:28,570 --> 00:18:37,750 So you have to think, how will you revive the cells from maybe mils or maybe 5200 mills? 148 00:18:38,080 --> 00:18:43,149 And then you have to think, then you have to bring it up to the next stage of the bioreactor. 149 00:18:43,150 --> 00:18:46,479 So it is a little two three litre engine next. 150 00:18:46,480 --> 00:18:51,130 You have to adapt it again into a bigger facility, just 200, 300 litre. 151 00:18:51,520 --> 00:18:57,280 And then we we can reach up to 4000 litre bioreactor volume. 152 00:18:58,330 --> 00:19:02,830 And then, of course, you have to think about how to clean those vessel. 153 00:19:02,890 --> 00:19:08,140 And then, uh, it would be better if you use a single use system. 154 00:19:08,300 --> 00:19:12,220 You don't really. I have to clean this stainless steel bioreactor. 155 00:19:12,220 --> 00:19:15,850 But yeah, this is a lot of consideration. 156 00:19:15,850 --> 00:19:22,090 And then how would you? Because we are supplying the nutrient to the cells with the menu. 157 00:19:24,010 --> 00:19:32,770 How would you transport your medium as sceptically inside the bioreactor? 158 00:19:33,310 --> 00:19:38,210 All sort of stuff to make all the process clean for the downstream. 159 00:19:38,230 --> 00:19:41,530 It's mostly about thinking about the filter size. 160 00:19:42,400 --> 00:19:47,920 And then how would you avoid the blockage of the filter? 161 00:19:49,240 --> 00:20:00,670 And then how would you achieve the highest purity of your product without disturbing the flow from the from the upstream? 162 00:20:01,420 --> 00:20:04,810 So you are always thinking about the continuous processing. 163 00:20:06,220 --> 00:20:09,250 Pretty interesting. Yes. Yes. Thank you for that. 164 00:20:09,790 --> 00:20:16,750 I think it's just very good background to everything that comes afterwards. This just makes it makes you understand how difficult it was. 165 00:20:17,560 --> 00:20:22,780 And so. Yes, so just to take to go to the next step in your career. 166 00:20:22,990 --> 00:20:26,920 How did you first hear about the job that was going here in Oxford? 167 00:20:27,640 --> 00:20:29,560 So it's a bit high. 168 00:20:31,410 --> 00:20:43,690 Yeah, it's and it's very weird because I actually I, I did my piece in Australia and then I actually haven't thought about going abroad, 169 00:20:43,870 --> 00:20:54,850 but when I was writing my thesis I found out about this work or working on manufacturing in the facility, which fits my skills quite well. 170 00:20:55,240 --> 00:21:01,990 I do in the other continent and this like quite far away from home. 171 00:21:01,990 --> 00:21:07,809 But I applied. So this is the facility that has been once here in Oxford. 172 00:21:07,810 --> 00:21:13,930 Is that the one you're talking about? Yeah. No, no. I'm working in gender bias. 173 00:21:14,080 --> 00:21:23,980 We are working closely with CBA. So in the description they required, I mean, they when in in in this era, I mean, 174 00:21:24,340 --> 00:21:33,940 there's not many people who who knows about the good manufacturing practice, especially a pasty graduate, freshly fresh graduate. 175 00:21:33,940 --> 00:21:45,970 But they put it in in the desired list of skills that if you know a lot about GMP, that it will be beneficial for this job. 176 00:21:47,080 --> 00:21:53,290 For this role. Mm hmm. And then so you didn't know any of the people here in the field, so you just applied? 177 00:21:53,560 --> 00:21:57,790 I just supply from the nature of jobs. Yes. So I would just search from the nature. 178 00:21:57,790 --> 00:22:01,810 And and it gives, like, a job for Taxman. 179 00:22:02,140 --> 00:22:06,660 And then I. I just send my application. Hmm. 180 00:22:07,720 --> 00:22:12,160 Well, clearly you've got that job. So, yes. You arrived here when? 181 00:22:12,160 --> 00:22:20,590 In 2019. Which is it? Yes, I arrive in the UK on 5th August 2019. 182 00:22:20,620 --> 00:22:23,770 Right. Okay. And what was the main work? 183 00:22:24,040 --> 00:22:27,580 What was the main kind of vaccine that they were working on at the time here? 184 00:22:27,790 --> 00:22:33,520 So at the time I was due to continuing the work of my colleagues. 185 00:22:34,420 --> 00:22:39,340 She had developed a single use process, 186 00:22:39,940 --> 00:22:48,880 up to three little process that can be this process can be used to produce small batches for the clinical trial at phase one. 187 00:22:49,570 --> 00:23:00,820 And at the time, my supervisor wanted to advance the manufacturing scale into maybe clinical phase two for phase three. 188 00:23:04,030 --> 00:23:07,359 That means. And this was using rabies vaccine. 189 00:23:07,360 --> 00:23:09,880 Yeah. This is still using the rabies vaccine. Yes. 190 00:23:10,120 --> 00:23:19,670 Because our group has a trial going on and you can then turn for clinical phase one and then the result is positive test. 191 00:23:19,730 --> 00:23:27,700 I can use thinking to move forward to the clinical phase two and three and he realised that and this is Sandy Douglas. 192 00:23:27,700 --> 00:23:35,920 Was Sandy Douglas. Yes, Sandy Sandy realised that the current process that my colleagues develop is not optimised yet, 193 00:23:36,550 --> 00:23:49,720 so they just simply making a GMP friendly process that quickly can be produced, can, can produce some batches just for the clinical trial, phase one. 194 00:23:50,020 --> 00:24:03,399 So my role is to optimise this process and also maybe this process can enough to supply for clinical trials to phase three, 195 00:24:03,400 --> 00:24:09,580 maybe for more than 10,000 doses, just like Novartis. 196 00:24:09,860 --> 00:24:18,850 To really a larger scale, like a 4000 litres come and be up to ten litres go into a GMP process that can be done in sea view. 197 00:24:20,120 --> 00:24:26,090 And how far had you managed to get with that by, say, the end of January 2020? 198 00:24:26,600 --> 00:24:27,350 You know what? 199 00:24:27,380 --> 00:24:38,180 So I started my working on this and this stuff and then by the end of November, I can see some results that I can optimise the upstream. 200 00:24:39,020 --> 00:24:51,770 So I find I found a formulation that can increase the productivity of the cells, making the virus by 15 times higher than in November. 201 00:24:51,770 --> 00:24:55,420 But with each cell could make 15 times much virus. 202 00:24:55,700 --> 00:25:02,180 That's right. By using a combination of nutrients. 203 00:25:03,020 --> 00:25:06,040 But I was still using Arabia's vaccine at the time. 204 00:25:06,050 --> 00:25:19,220 Yes. Yeah. Mm hmm. And in in December, actually, I, I went back to Australia to attend my graduation and I went back in only January 2020. 205 00:25:20,240 --> 00:25:29,690 Yeah. And then at the time, you know, this is the first time I heard about, uh, the, uh, the outbreak in China. 206 00:25:29,960 --> 00:25:33,050 Yeah, that was my, that was my going to be my next question. 207 00:25:33,050 --> 00:25:38,600 So what how can you remember where you were when you first heard about it and 208 00:25:38,930 --> 00:25:42,590 how soon you realised that it was going to have a very big impact on your work? 209 00:25:42,870 --> 00:25:48,889 I still do. First, I heard it when I was in the lab where me and Sandy and Sophia, my former colleague, 210 00:25:48,890 --> 00:26:05,299 was talking about it and and Sandy gave me Sandy was mentioning that maybe you will be working with the SARS-CoV-2 vaccines quite soon, 211 00:26:05,300 --> 00:26:14,940 but I didn't think much of it. I said, okay, then it's interesting to work on the hottest topic at the moment because I mean, 212 00:26:15,120 --> 00:26:18,590 we work in the rugby, but again, this is not a really popular topic. 213 00:26:20,210 --> 00:26:23,210 It's not really a problem in Western countries, is it? 214 00:26:23,210 --> 00:26:32,360 It's much more a developing country. This wasn't a problem in developing countries, but this is important, but it's a problem not in this country. 215 00:26:33,500 --> 00:26:42,620 And yeah, at the time I was still working with the very small scale cells, maybe around 30 million, the Zika, I don't think much of it. 216 00:26:44,390 --> 00:26:50,090 And then Sandy saying, oh, maybe you will be working with the latest vaccine. 217 00:26:50,090 --> 00:26:59,840 But I thought he was just saying it and things probably move pretty quickly after that. 218 00:27:00,260 --> 00:27:14,050 Yeah, yeah, yeah. And in the end, I think in January 2020, uh, I remember like Sandy saying that, okay, 219 00:27:14,120 --> 00:27:22,370 I think we and the problem in China has become bigger and then it may become a pandemic. 220 00:27:22,460 --> 00:27:33,340 I hate to keep mentioning this li me it would be uh, uh, the biggest problem after the Second World War. 221 00:27:33,500 --> 00:27:41,330 I thought he was joking, you know, and I said, Yeah, we only heard it quite far in Wuhan, very spreading. 222 00:27:41,990 --> 00:27:47,240 Spreading a little bit. But it's not actually a big problem in UK yet. 223 00:27:47,900 --> 00:27:58,190 Maybe still be a problem, but we have to track the progress of the sprint in UK and and. 224 00:27:58,730 --> 00:28:10,880 Yeah, and then in early February 2020, he wanted me to dress like a 200 litre production, gmp, 225 00:28:11,990 --> 00:28:17,600 gmp production of this vaccine, which this is, this was the vaccine that had been made by itself. 226 00:28:17,600 --> 00:28:20,710 The Sara Gilbert scoop. Yeah. I mean. Yeah. 227 00:28:20,750 --> 00:28:25,850 In the gender. Yeah. Yes. Uh, the, I think in Jenner 2020, 228 00:28:25,850 --> 00:28:37,040 he already talked to all of the group leader in gender that they have to be prepared in if there is any pandemic or outbreak in UK, 229 00:28:37,340 --> 00:28:40,219 they have to have at least small batches of virus. 230 00:28:40,220 --> 00:28:48,560 And and I think they started making the plasmid for this virus in January 2020 and then February 2020. 231 00:28:48,560 --> 00:28:53,680 They actually have some made my final vector vector. 232 00:28:54,500 --> 00:29:02,360 So they have a small JLP, uh, standard of this vaccine. 233 00:29:03,420 --> 00:29:08,569 And the, the, the vehicle they were using was the same as the one you've been using for the rabies. 234 00:29:08,570 --> 00:29:11,620 Is that right? It's. It's similar. 235 00:29:11,800 --> 00:29:17,680 It's similar. But the one that I'm using is the second generation, right? 236 00:29:17,770 --> 00:29:28,890 Yeah. Backbone is called the one that was used for making this SARS-CoV-2 vaccine is the first generation of this kind of swine. 237 00:29:29,140 --> 00:29:32,500 So slightly different, but a similar back one. 238 00:29:32,500 --> 00:29:35,690 But there's a couple of amino acid sequence difference. 239 00:29:35,720 --> 00:29:42,190 Okay. So but in this case, they are the same chimpanzee adenovirus vector. 240 00:29:42,220 --> 00:29:50,560 Yep. So how challenging was it to think of getting up to 200 metres? 241 00:29:51,190 --> 00:29:54,220 Well, firstly, we don't have any equipment to do so. 242 00:29:54,730 --> 00:29:58,480 And I was, I was thinking he's kidding. 243 00:29:58,480 --> 00:30:03,520 Or I was. Yeah, I thought he was really kidding. 244 00:30:05,170 --> 00:30:13,390 Oh we have in, in our lab is very traditional bioreactor that is very old. 245 00:30:14,800 --> 00:30:20,200 And this what I want my impression was because I came from a quite fully 246 00:30:20,200 --> 00:30:26,380 equipped laboratory in Australia and then I came here and then the laboratory, 247 00:30:27,010 --> 00:30:31,480 laboratory space is quite small first of all, and the equipment is quite old. 248 00:30:32,230 --> 00:30:46,180 Uh, for that to just make do for the, in 2019, I just make, do all of the equipment just to have enough process to go on with. 249 00:30:46,690 --> 00:30:55,329 So it's, I don't think it can be, uh, translated into 200 metre at the point. 250 00:30:55,330 --> 00:31:06,909 And then, then we have to build a really new system with completely new equipment for the later process, and that would be expensive. 251 00:31:06,910 --> 00:31:08,430 So you need some money from something. Yes. 252 00:31:08,920 --> 00:31:18,400 And then that's why I contacted all my colleagues in Australia asking a lot, pressing for everything, for bioreactor, 253 00:31:18,730 --> 00:31:28,060 for the filter and for actually establishing the lab from the scratch when it come up to a few million pounds. 254 00:31:29,710 --> 00:31:42,720 And then I us sending do we have this much budget to quickly established this type of the lab and then he just cross a few of it and then uh, 255 00:31:42,820 --> 00:31:48,330 reducing some of the cost down. So we actually, uh, 256 00:31:49,390 --> 00:32:00,730 thinking to produce the best bench on LP scale from the first in the Wellcome Centre lab 257 00:32:02,200 --> 00:32:09,700 utilising all of the material we have actually we can use 50 litre scale bioreactor with those, 258 00:32:09,700 --> 00:32:18,969 bioreactor with those generator, but uh, we still haven't got any, yeah, 259 00:32:18,970 --> 00:32:28,060 we still haven't got any supplier that agree to supply us with bioreactor and the filter and the time. 260 00:32:31,100 --> 00:32:38,030 So. Yeah, so I thought, yeah, I don't think we can do this. 261 00:32:38,360 --> 00:32:54,770 And then and that I'm the one who has the skill in the upstream and knows how to do to run the biotech in a GMP controlled environment with only me. 262 00:32:55,850 --> 00:33:01,060 And then the research assistant that we have is not trained to do that. 263 00:33:01,340 --> 00:33:07,909 So you felt a bit lonely? I was thinking I never met this guy. 264 00:33:07,910 --> 00:33:20,080 No supervisor. Just give me a project on the spot to do it in such a limited and you know, and deadline is impossible deadline. 265 00:33:20,840 --> 00:33:24,570 So I say here. So how did you work it out between you where you were? 266 00:33:24,660 --> 00:33:29,660 You demonstrated to him that it wasn't possible to do in the time with the funding you had available. 267 00:33:30,110 --> 00:33:34,430 You wouldn't hear about it still puts on the schedule. 268 00:33:34,880 --> 00:33:45,060 And then thankfully and then he realised that we actually could and couldn't do the 50 litre and 200 litres 269 00:33:45,440 --> 00:33:52,340 in our lab because it's really small and then we really need a quite a big space to accommodate that. 270 00:33:53,630 --> 00:34:02,930 And then he started gathering, meeting some company to help us in scaling up the process. 271 00:34:03,860 --> 00:34:15,229 So there are few companies that are willing to help us to simulate our process in the lab that's already been established. 272 00:34:15,230 --> 00:34:20,480 We could we could establish a new lab in such a short period of time. 273 00:34:21,050 --> 00:34:30,780 So yeah, I think from many commercial company, we decided to collaborate with Paul in Portimao. 274 00:34:30,800 --> 00:34:33,830 That's part yes, yes, yes, yeah. 275 00:34:34,040 --> 00:34:37,910 Yeah. I was that your first experience of collaborating with a commercial company? 276 00:34:38,240 --> 00:34:44,840 Oh, no. I mean, I collaborated a lot with a lot of pharmaceutical company like Paul McArthur is back in Australia. 277 00:34:44,900 --> 00:34:56,600 Oh, this is my first time in UK. Yeah, that I had the chance to actually work in a big project, which is not really well planned in the beginning. 278 00:34:59,270 --> 00:35:00,500 Mm hmm. Okay. 279 00:35:01,610 --> 00:35:12,320 So in February 2020, I get to work with the actual COVID vaccine virus, and then I tested in fairly small scale, same like what I did in 2019. 280 00:35:12,810 --> 00:35:19,549 And then I know the process works and then I go, and you're your way of making the cells work faster. 281 00:35:19,550 --> 00:35:25,100 Worked with the new virus as well. Yes, that's right. So we could improve the productivity significantly. 282 00:35:25,610 --> 00:35:38,210 And with this combination of upstream, the cells behave really well in the larger scale compared to the previous process. 283 00:35:38,570 --> 00:35:43,220 And then now the bottleneck is in the downstream. 284 00:35:44,240 --> 00:35:53,150 So we keep the same process as the the process before before I joined the team. 285 00:35:53,870 --> 00:36:04,070 One really lesson we got to we had such a high productivity, we couldn't really concentrate the volume that was in the downstream. 286 00:36:05,810 --> 00:36:13,610 So we need to modify the downstream little we talk only the number of vaccine doses in the volume. 287 00:36:13,760 --> 00:36:18,919 I see. That's because there's more vaccine in the same volume and you've got to love it again. 288 00:36:18,920 --> 00:36:27,410 It's a flow problem, presumably, and this a concentration problem because with this vaccine they get they don't want to be concentrated 289 00:36:29,990 --> 00:36:36,620 at the certain level or else they will aggregate which which will cause us the loss of the vaccine. 290 00:36:36,620 --> 00:36:44,690 Right. So they actually have to be spread. This is the cells that need to be spread of the virus, although the actual virus back to the virus. 291 00:36:46,020 --> 00:36:59,569 Yes. So in the industrial after we separate that the cells from the virus and the forest needs to be in a certain density higher than that level, 292 00:36:59,570 --> 00:37:06,440 then the virus will the vaccine will aggregate and it will not go to the filtration. 293 00:37:06,440 --> 00:37:09,530 So there'll be a loss of vaccines. Yes. Yes. 294 00:37:09,530 --> 00:37:15,140 The thing is. So with that, just a matter of using bigger vessels or dividing it into more vessels. 295 00:37:15,440 --> 00:37:24,440 And we need to modify the process so we cannot concentrate more than before. 296 00:37:24,680 --> 00:37:30,050 Before the process is like. Include the concentration step into. 297 00:37:31,300 --> 00:37:36,610 Ten times concentration, then we know we have to change it to only two times concentration, 298 00:37:36,970 --> 00:37:41,200 but then means we have to accommodate more volume in the purification step. 299 00:37:43,570 --> 00:37:51,520 Yeah. And then then we bring that process in to how we write the protocol. 300 00:37:51,520 --> 00:38:01,940 And then we tell. We train the scientists in our cloud lab on how to do which lab. 301 00:38:01,970 --> 00:38:05,120 Sorry. In Portimao. Oh, that's what it is. 302 00:38:05,140 --> 00:38:08,709 Yeah. Yeah, it's called Paula Partition. 303 00:38:08,710 --> 00:38:16,690 Portimao. So firstly, to transport the virus and the cells. 304 00:38:16,990 --> 00:38:20,979 Oh, my project. 305 00:38:20,980 --> 00:38:24,250 And I just have to drive to work out, which is. 306 00:38:24,670 --> 00:38:32,050 Is it right at the end of Cornwall or is it how far to hold it? I don't know what it is, but I think it's 3 hours was a long way. 307 00:38:33,080 --> 00:38:42,280 I remember that because we don't have time to send them a liquid nitrogen file, 308 00:38:42,670 --> 00:38:50,800 which it will take a couple of weeks to refine the cell into the volume that we wanted. 309 00:38:51,130 --> 00:38:58,720 So we actually just take a three litre flask with a one litre portfolio in the shaking flow. 310 00:38:58,720 --> 00:39:05,040 And my manager had to drive from this this lab into the apartment lab. 311 00:39:05,890 --> 00:39:11,440 He took his assistants, uh, just to check the cells. 312 00:39:14,650 --> 00:39:22,150 Well, he has to recheck inside the Styrofoam box because the cell has to be kept at certain temperature, like 57 degrees. 313 00:39:22,750 --> 00:39:31,920 So. So, so I have I fill it up with a 37 degree water water bottle for a yeah, for the warm. 314 00:39:31,960 --> 00:39:36,310 And then she has to check it every 3 minutes. All the way to go. 315 00:39:37,450 --> 00:39:42,819 Yeah. All the way to now and then at the time there was a lockdown. 316 00:39:42,820 --> 00:39:52,870 So yeah, I mean I have to work in the lab by myself and, and there's no nobody also in the road because there's a lockdown. 317 00:39:53,230 --> 00:39:57,910 And in particular, I was scared that you will be stopped by a police or something, 318 00:39:58,240 --> 00:40:06,070 but you had to get a letter saying and we are doing a very important work and please don't stop. 319 00:40:07,810 --> 00:40:11,780 But that letter might be something that the Bodleian would like to collect a copy of that letter. 320 00:40:11,800 --> 00:40:14,140 I think maybe if it still exists. 321 00:40:14,290 --> 00:40:21,399 Yeah, I should, I don't know where he put it, but and possibly even the Styrofoam box with the, with the, with the vessel inside, 322 00:40:21,400 --> 00:40:26,920 I mean, it doesn't have to have the virus in, but I think it's a wonderful story and I hadn't heard that before. 323 00:40:27,040 --> 00:40:33,250 Oh, yeah. So there's a starter, the starter cells that to sit the bioreactor. 324 00:40:33,730 --> 00:40:44,889 So in in in the lab in Portland we agreed that they will do two trial of production run to mimic our process. 325 00:40:44,890 --> 00:40:49,420 The first scale that they will do is the 50 litre and then two litre scale. 326 00:40:50,050 --> 00:40:57,100 So how after February 2020, I think they give us a deadline. 327 00:40:57,910 --> 00:41:05,410 By end of March 2020, they have to start the first production run, which is the 50 litre one. 328 00:41:07,300 --> 00:41:14,500 So so at the time in February 2020, we didn't have any process to go. 329 00:41:15,130 --> 00:41:21,760 So all of the upstream process is new and then we have to also slightly modify the downstream. 330 00:41:23,770 --> 00:41:29,140 So I actually I only have like one and half months to design the whole process which 331 00:41:29,440 --> 00:41:35,860 normally would take a whole team consist like 3 to 4 people a few years to make. 332 00:41:35,860 --> 00:41:39,579 Goodness me. Yeah, that's extraordinary. 333 00:41:39,580 --> 00:41:48,459 This is but but I mean I know that Sunday was saying had already I think even by the end 334 00:41:48,460 --> 00:41:55,540 of January set out a timetable that would lead to a national rollout of the vaccine. 335 00:41:55,600 --> 00:42:03,990 Yes, we have a vaccine ready by this time in less than a year, which again, would be, you know, five times faster than it had ever been done. 336 00:42:04,120 --> 00:42:08,829 So, yes, I think I mean, to to get that grant, 337 00:42:08,830 --> 00:42:17,460 I think he has to make those timetable to envision what will happen in the future if the vaccine will go through the clinical trial. 338 00:42:18,250 --> 00:42:24,100 Yeah, well, yes. Like you set up a deadline, which is, uh, very tight. 339 00:42:25,030 --> 00:42:28,660 Yeah. And you made that end of March deadline, presumably? 340 00:42:28,930 --> 00:42:34,750 No, no, we had to, because this this the only time slot that we were given. 341 00:42:35,080 --> 00:42:41,690 Then, of course, they're really being very generous because they. 342 00:42:42,090 --> 00:42:46,140 A space to us with with no costs. 343 00:42:46,620 --> 00:42:51,350 And then they also supply a lot of consumables to us and goodwill. 344 00:42:51,630 --> 00:42:56,610 Mhm. Yeah. So we had to make do because they were empty and in the slots. 345 00:42:56,650 --> 00:43:12,300 Yeah. For us. And then we quickly developed the process and the whole manufacturing process and, and we uh we convey what they have to do and then, 346 00:43:12,780 --> 00:43:22,860 and, and also we had a lot of phone calls with them and then, uh, do a lot of troubleshooting how to do the process in the larger scale. 347 00:43:24,210 --> 00:43:29,410 And they help us by writing all of the documentation, 348 00:43:30,060 --> 00:43:41,700 and that is enough to be transported for G and be processed and all of the parameters written down for them. 349 00:43:42,030 --> 00:43:51,030 And then yeah. And this little run was, uh, runs quite smoothly because uh, 350 00:43:51,510 --> 00:43:59,670 in the first instance they stick to what the process that they can do, then it, it makes quite a lot of virus. 351 00:44:02,210 --> 00:44:05,960 And what was the first use that was used for the phase two? 352 00:44:06,230 --> 00:44:12,350 No, I think because this production process is still not under GMP. 353 00:44:14,090 --> 00:44:22,880 So the the lab that they have is not a GMP approved laboratory, but the process that they've done is the GMP. 354 00:44:23,180 --> 00:44:34,400 So actually, they've already done a GMP process in the controlled material, but just the facility itself is not the GMP approval. 355 00:44:34,760 --> 00:44:39,440 So it's not the list. This device cannot be used in humans. 356 00:44:39,680 --> 00:44:45,110 So it was a demonstration. It was positive demonstration. Yeah, we can produce that much vaccine doses. 357 00:44:45,500 --> 00:44:55,870 And then that's also a foolproof process that this process can produce this much of vaccine. 358 00:44:56,210 --> 00:45:02,690 And then as a projection, how much doses we can produce in one facility. 359 00:45:04,520 --> 00:45:17,239 And then but at the time, because this the only large scale vaccine that's been produced in maybe UK or in the world, we also story in there. 360 00:45:17,240 --> 00:45:22,430 They send us enough vaccines and actually the vaccine one project. 361 00:45:22,440 --> 00:45:28,460 Why do you say it's if it's emergency, Jesse, maybe we can use this vaccine because it's it's clean. 362 00:45:29,210 --> 00:45:39,350 Yeah. And I think we have, like, quite, like, 200,000 doses sent from that lab to gender. 363 00:45:40,040 --> 00:45:45,680 And I saw it in the -80 degree freezer here, and that's still there. 364 00:45:46,730 --> 00:45:49,990 We use it for standard. And so far. Yes, yes. 365 00:45:50,300 --> 00:45:53,920 You sit with my bed. I still have some gas. Yeah. Yes. 366 00:45:54,110 --> 00:46:03,560 And I still have some of they are liquids. So were you able to take a bit of a breath at that point or were you still just as busy? 367 00:46:04,190 --> 00:46:07,459 Oh, okay. No use. Just getting busier. 368 00:46:07,460 --> 00:46:14,540 I mean. Yeah, all all the main team which is Sandy, my supervisor, Sandy Douglas, 369 00:46:14,750 --> 00:46:25,310 the official from Sandy Douglas is mainly doing presentations or meetings with a lot of our collaborators. 370 00:46:25,790 --> 00:46:37,909 And Dr. Adam Ritchie, the project manager, was dealing with a lot for contracts and commercial dealing and and I'm actually in charge in the lab. 371 00:46:37,910 --> 00:46:45,830 So those three people are the main people in this project involving the manufacturing. 372 00:46:46,640 --> 00:46:52,160 So we all work for 16 to 18 hours a day, seven days a week. 373 00:46:53,840 --> 00:46:59,030 And then this was just the beginning of the, the vicious work schedule. 374 00:46:59,720 --> 00:47:06,709 And then, uh, yeah, I mean, yeah, I mean, that's the one half year away. 375 00:47:06,710 --> 00:47:13,190 We don't have enough. And then we didn't get any break for a year and a half and one year and a half. 376 00:47:13,920 --> 00:47:20,840 That's very tough. Very tough. And then after that, after the fifth little was successful. 377 00:47:21,200 --> 00:47:32,240 We had to scale up to 200 little. And there's some problem with the 200 later because they don't have capacity to do that much of volume. 378 00:47:32,630 --> 00:47:38,690 So there's a gap within the upstream and downstream, which we would not recommended. 379 00:47:39,500 --> 00:47:47,209 But actually we were the proof that the process will also work in later as long as you follow all all 380 00:47:47,210 --> 00:47:58,290 of the protocol and after the two and a little run we sorry they did the 200 litre at full status. 381 00:47:58,580 --> 00:48:00,950 Yeah. What with the larger bioreactor. Right. 382 00:48:03,020 --> 00:48:13,310 And then after that we were, they characterise our process then we can now compile all documentation into a GMP, 383 00:48:15,320 --> 00:48:23,150 GMP protocol that we can distribute to all of our called lab collaborators, 384 00:48:23,480 --> 00:48:29,630 which is the GMP commercial manufacturing facility and this involving in our consortium. 385 00:48:30,860 --> 00:48:36,820 So I think Selby set up CMO, a contract manufacturing organisation. 386 00:48:36,830 --> 00:48:50,870 Oh, right. Oh yes. So they are a commercial entity that agreed to produce the vaccines, uh, as long as they are involved in this commercial dealing. 387 00:48:51,260 --> 00:48:56,930 So there are some I think one of it is Oxford BIOMEDICA. 388 00:48:57,140 --> 00:49:00,320 Oh, yes, yes. Yeah. The Serum Institute of India. 389 00:49:00,470 --> 00:49:03,800 There's some. There was a company called Cobra. 390 00:49:04,820 --> 00:49:15,800 Helix. Yeah. So after we had the documentation, we can distribute them to all of this year. 391 00:49:15,810 --> 00:49:26,700 Also, they can have the protocol and we could start making all of the ingredients, which is to the GMP level. 392 00:49:26,750 --> 00:49:34,850 The first thing is we need to make a master cell banks, which has to be done under the GMP conditions. 393 00:49:34,850 --> 00:49:42,350 So I think COBRA is making Cobra meet the master cell banks and I think Helix making the seed virus. 394 00:49:44,210 --> 00:49:50,840 So all of the ingredients were made in under a GMP condition. 395 00:49:51,230 --> 00:49:57,380 Then all of the cells and the forest can be distributed to a lot of other similar. 396 00:49:58,700 --> 00:50:08,839 So they can also start making the vaccines and where you constantly having calls with all these other companies to see if they had problems. 397 00:50:08,840 --> 00:50:18,800 And yeah, I mean, I at the time I had to do the legwork and I also have to join the meeting. 398 00:50:19,430 --> 00:50:22,580 And then in the meeting there'll be a lot of company. 399 00:50:23,090 --> 00:50:30,920 So representation of the company, asking a lot of questions of troubleshooting, a lot of problem in the lab. 400 00:50:31,160 --> 00:50:37,880 And then I had to be able to provide an answer and, and help them guide them on how to overcome their troubles. 401 00:50:39,590 --> 00:50:47,840 And then we have and end the point we have, we have a process to make the functions in 200 litre. 402 00:50:47,840 --> 00:50:57,770 But just like the work of going to 200 litre but 200 litre volume, 403 00:50:58,850 --> 00:51:10,489 we see some bottlenecks in going to to handle a litre because firstly we have a lot of fires coming 404 00:51:10,490 --> 00:51:16,460 from the upstream and then we still keep some of the process similar to the previous process. 405 00:51:16,850 --> 00:51:21,350 But one of the step in the downstream cannot really be done in the larger scale. 406 00:51:22,670 --> 00:51:35,899 So at the time we had to develop our downstream and then make it into a new downstream process that can accommodate our process in 2000 plus litre. 407 00:51:35,900 --> 00:51:38,350 So. All right. Yes, he takes care. 408 00:51:38,540 --> 00:51:46,010 So one of the first industrials called Drove, which is tangential flow filtration, basically did say that again, it was loaded. 409 00:51:46,370 --> 00:51:49,570 But this is DMF is tangential flow. 410 00:51:49,580 --> 00:52:01,670 Tangential flow filtration. Yes, right. This means when you when you pump and the liquid or the flow, 411 00:52:02,030 --> 00:52:08,600 it would it should not go directly to the membrane, but it will go in parallel with the membrane. 412 00:52:09,080 --> 00:52:15,020 But some of the element inside the liquid will traverse through the membrane. 413 00:52:16,880 --> 00:52:22,760 This one, because it is not linked directly, directly to the membrane, but it's just in parallel with the membrane. 414 00:52:23,180 --> 00:52:31,069 So the principle in tangential for filtration is concentration and filtration once again, 415 00:52:31,070 --> 00:52:39,070 because we couldn't really concentrate our downstream instead of tendon construction, we had to do two times concentration instead. 416 00:52:39,740 --> 00:52:45,290 So the the volume from the upstream and downstream is really large. 417 00:52:47,030 --> 00:53:03,080 And then it we couldn't do that process in a thousand litre plus because one, they don't have that big storage enough for for holding the capacity. 418 00:53:03,380 --> 00:53:10,700 Also that means they need a fairly large amount of buffer to do the process. 419 00:53:12,050 --> 00:53:20,090 So to do a thousand litres of volume of production in the afternoon, then we would need 10,000 litres of buffer. 420 00:53:20,780 --> 00:53:29,750 So they couldn't house that in that lab because if I will be the selection of space, not the footprint. 421 00:53:29,810 --> 00:53:37,639 Yes. And also the pump that they need to use in that process. 422 00:53:37,640 --> 00:53:49,760 They have to have like around 2500 litres per per hour or something, so they don't have that much of capacity in the facility. 423 00:53:50,540 --> 00:54:01,250 So preventing us to go to even in the larger capacity, which is actually if we go into larger capacity, is beneficial for us because we could make. 424 00:54:01,450 --> 00:54:03,580 More vaccine doses in one batch. Yes. 425 00:54:04,150 --> 00:54:14,950 And and the time and in that period of time is really necessary because then we don't have enough vaccine supply to supply the world and even UK. 426 00:54:16,450 --> 00:54:26,710 So we really would like to go to a higher volume what our process limiting is limiting to 200 litre. 427 00:54:27,010 --> 00:54:40,090 So we we make a new strategy on skipping that first step of purification, but we still keep the quality of the vaccines at the same standard. 428 00:54:41,440 --> 00:54:49,389 So we started changing the dosing and for that we need to generate a lot of data for the proof of concept. 429 00:54:49,390 --> 00:54:58,810 Yeah. So the process can be tested in a thousand litre without wasting any of the components. 430 00:54:59,500 --> 00:55:04,870 So that's what I'm doing in within that timeline. I'm testing the new process in our lab. 431 00:55:04,900 --> 00:55:11,110 Yeah. And you're generating a lot of data and communicating the data to all of our collaborators, 432 00:55:11,230 --> 00:55:16,660 especially the CMO who has like a thousand litre plus capacity. 433 00:55:18,790 --> 00:55:21,999 So that it was an enormous amount of work to do. 434 00:55:22,000 --> 00:55:28,640 But having done that, that will be beneficial in future, presumably for other kinds of vaccine as well, 435 00:55:28,660 --> 00:55:32,890 that it'll speed up the process of producing large volumes. 436 00:55:33,070 --> 00:55:33,730 And that's right. 437 00:55:34,040 --> 00:55:46,449 The benefit of this process is because it's applicable to all sort of channels, which is to identify a factor which can be this factor. 438 00:55:46,450 --> 00:55:52,090 Technology can be used to make a lot of different vaccine for different pathogen. 439 00:55:52,480 --> 00:56:03,370 So the process doesn't have to be maybe needs to be adaptive, but it doesn't need to be changed tremendously. 440 00:56:03,850 --> 00:56:09,520 Just need to be slightly adapted to manufacture different vaccine. 441 00:56:12,120 --> 00:56:24,580 So having succeeded in getting the, the larger capacities that then went that then went into the clinical trials presumably. 442 00:56:24,910 --> 00:56:29,320 Yeah. Yeah. Did you did you ever have time to think. 443 00:56:30,010 --> 00:56:35,500 Yes, we've we've done it. We were always onto the next the next thing. 444 00:56:35,890 --> 00:56:40,900 Did you allow yourselves to celebrate your small victories along the way? 445 00:56:41,950 --> 00:56:56,079 I mean, I really I don't think I have a moment of celebration because at the time the work is keep piling up because we have many things to do, 446 00:56:56,080 --> 00:56:59,980 tests in the in the lab. And then you have to generate a lot of data. 447 00:57:00,190 --> 00:57:08,920 And the work doesn't only stop at that point because after then we also generating another two year fun. 448 00:57:09,730 --> 00:57:21,210 So in order to make even more vaccines and then, you know, because there's a lot of experiments scheduled, 449 00:57:21,220 --> 00:57:27,280 I don't have time to actually stop and think about anything or celebrate anything. 450 00:57:27,280 --> 00:57:31,480 I it was just like I was in like a hamster. 451 00:57:32,710 --> 00:57:40,510 Yes. And then all all of things that are happening outside the lab, it's just like another world to me. 452 00:57:40,840 --> 00:57:47,000 So my world is only inside the lab. Mm hmm. 453 00:57:47,150 --> 00:57:53,500 I'm going to ask you some more questions about that later, but. Yes. 454 00:57:53,500 --> 00:57:57,670 I mean, I. I think I've asked that. So how. 455 00:57:57,910 --> 00:58:03,580 I mean, we you know, we now know that the vaccine was developed and it has been implemented all over the world. 456 00:58:04,390 --> 00:58:10,340 Was it important to you personally that the vaccine should be available to people in low and middle income countries? 457 00:58:10,360 --> 00:58:16,170 Was that something that you thought of that? Yeah. I mean, this was our purpose from the beginning. 458 00:58:17,650 --> 00:58:24,070 Yeah. I mean, we all with the vaccines. So I think fixing inequities in the world. 459 00:58:24,370 --> 00:58:34,810 But I came from the lower middle income country. And I also wanted my people from from my country to have access to the vaccines. 460 00:58:35,260 --> 00:58:45,130 And then for that purpose, we would like to make these vaccines affordable to everybody and to be able to produce 461 00:58:45,390 --> 00:58:49,960 a lot of vaccine in a very short period of time so they can actually have timely, 462 00:58:50,470 --> 00:58:56,250 uh, uh, timely vaccines. 463 00:58:57,520 --> 00:59:02,560 Uh, I mean, so they can receive the vaccine in a timely manner. 464 00:59:02,700 --> 00:59:12,100 Mm hmm. And that's I mean, the the Oxford vaccine has been the one that's been most used in low and middle income countries. 465 00:59:12,120 --> 00:59:20,670 Yes. Yes. I mean, we are the biggest supplier for the products and we are in this, 466 00:59:21,590 --> 00:59:31,770 I think the total pertussis vaccine like 1.5 billion doses, and it's still being manufactured now. 467 00:59:32,430 --> 00:59:36,780 Ms. 13 Is that mostly from Serum Institute of India? 468 00:59:36,780 --> 00:59:39,809 Is that the biggest from this era of our effectiveness in India? 469 00:59:39,810 --> 00:59:40,920 Serum Institute of India? 470 00:59:41,730 --> 00:59:50,190 Well, we have collaborated with 25 different manufacturing facilities in five different continents, in 15 different countries. 471 00:59:50,610 --> 00:59:55,140 And most of our vaccine is actually being produced in low and middle income countries. 472 00:59:55,220 --> 01:00:02,280 All right. So it has a lot with the vaccine equity because, you know, 473 01:00:02,280 --> 01:00:08,430 when the vaccine is produced in that country and in that country and that particular 474 01:00:08,820 --> 01:00:13,800 pharmaceutical company has the right to decide who will receive the vaccine. 475 01:00:14,910 --> 01:00:27,210 So because of our focus in manufacturing in low income countries that miss surrounding country will also have an immediate access to the vaccines and. 476 01:00:31,040 --> 01:00:36,440 And have you have you done any travelling since it became possible to do so? 477 01:00:36,470 --> 01:00:42,140 Have you visited some of these manufacturing sites? I haven't gone far. 478 01:00:42,150 --> 01:00:52,160 I haven't gone to India or China, but I have visited the the laboratory in. 479 01:00:53,030 --> 01:00:57,480 I'm in France. Yeah. You've not been home to Indonesia? 480 01:00:57,630 --> 01:01:01,520 No, I haven't got back to Indonesia. Yeah. 481 01:01:02,030 --> 01:01:04,610 So you're still so what do you what are you mainly working on now? 482 01:01:05,300 --> 01:01:21,770 So now I'm we still continue on for there improving our manufacturing process and the first instance in 2020, the goal of our project is simplicity. 483 01:01:22,640 --> 01:01:32,870 So in order for the low middle income country to be readily accept our manufacturing process, 484 01:01:33,440 --> 01:01:39,800 then we couldn't really design quite a complicated process for the manufacturing. 485 01:01:40,070 --> 01:01:44,540 We want them to immediately be able to produce the vaccines. 486 01:01:45,800 --> 01:01:51,890 So, uh, so I designed the process for, uh, 487 01:01:52,670 --> 01:02:01,190 to enforce simple enough for those type of wonderful filling facility to top our process and start making the vaccine. 488 01:02:01,210 --> 01:02:09,560 So because it's the pandemic time enough, they're after a few million doses from this. 489 01:02:10,010 --> 01:02:15,470 So we have enough freedom to introduce some complexity to our process. 490 01:02:15,860 --> 01:02:21,680 That means we can introduce more complex equipment and process which can 491 01:02:22,340 --> 01:02:29,180 significantly improve our yield in terms of vaccine doses in the single batch. 492 01:02:30,470 --> 01:02:38,720 So I'm working on the new technology to produce more vaccines in the shortest one period of time in a single batch. 493 01:02:39,890 --> 01:02:44,420 And does that relate both to rabies and to COVID, or are you still focusing on COVID? 494 01:02:44,510 --> 01:02:50,600 I am. I'm applying this process in many other vaccines, including the obvious, right? 495 01:02:51,410 --> 01:02:56,540 Yep. And have you got your working hours under control or so? 496 01:02:56,930 --> 01:03:00,470 I was, and I would hope so. 497 01:03:00,560 --> 01:03:06,070 I mean, I. I think I still have to work with my work life balance. 498 01:03:07,880 --> 01:03:12,620 I think I'm a I'm quite a workaholic. 499 01:03:12,620 --> 01:03:15,620 So if I have something to do, I will do it. 500 01:03:15,890 --> 01:03:22,400 No matter what the time is, the night or weekend are still I still feel like I have to come and do it. 501 01:03:22,400 --> 01:03:25,610 But it's it's getting much better from the last year. 502 01:03:25,730 --> 01:03:29,570 I mean, I can go home and sleep well. 503 01:03:29,570 --> 01:03:35,389 You're not going home before. Were you just not sleeping when you got there? Yes, I'm from some of the time. 504 01:03:35,390 --> 01:03:46,820 I mean, I sometimes I maybe I in 2020 and some of the day I just go back home and take a shower and then go back again. 505 01:03:47,000 --> 01:03:51,620 I just need to collect some juice. Yeah. And then continue the next morning. 506 01:03:52,070 --> 01:03:55,070 But nowadays I don't have to do that. So I have. 507 01:03:55,970 --> 01:04:05,120 I have enough time to sleep well. Um, yeah, I've, we've talked about it quite a lot. 508 01:04:05,120 --> 01:04:16,840 We can go on from that. Yeah. 509 01:04:16,850 --> 01:04:28,840 I mean. I've got a question about whether you think the changes that the lockdown made to the way everybody was able to work, 510 01:04:31,090 --> 01:04:37,360 did that have any positive effects? I mean, for example, things like remote holding meetings remotely and so on. 511 01:04:37,750 --> 01:04:44,530 Is that something that has proved to be beneficial even now that it's not necessarily something you have to do anymore? 512 01:04:45,610 --> 01:04:54,420 I think in the beginning, I never know how to use the technology like Zoom or Microsoft teams, 513 01:04:55,060 --> 01:05:03,700 and now it's really convenient, even if I couldn't attend the meeting directly, but I can still doing the meeting by online. 514 01:05:04,570 --> 01:05:07,750 But I think it's a good technology to have. 515 01:05:08,200 --> 01:05:15,370 I mean, now nowadays this you can attend a lot of online conference without having to be there while still doing your work, 516 01:05:16,180 --> 01:05:20,800 just listening to the important information that we have there. 517 01:05:21,700 --> 01:05:35,410 But yeah, for the most part, I still miss being attending meeting face to face because I think we do need some human interaction. 518 01:05:36,010 --> 01:05:43,540 Yes, yes. Yeah. Yeah. And what's I mean, you've talked about your work life balance, which sounds terrible. 519 01:05:45,190 --> 01:05:49,660 Did you was there anything that you did to support your personal wellbeing? 520 01:05:50,380 --> 01:05:53,770 I mean, how did you keep going? How did you not have a breakdown? 521 01:05:54,220 --> 01:06:01,840 I would survive. I mean, when I had the breakdown in those 20, 20 time. 522 01:06:01,840 --> 01:06:08,110 But thankfully, I have I would think that I have quite a supportive team, 523 01:06:09,340 --> 01:06:17,080 like I have my project manager that I talk regularly with and discuss my problem with my boss, 524 01:06:17,410 --> 01:06:27,250 even though like, yeah, we have like a different interaction and he's my boss and, and he wanted the work to be done. 525 01:06:27,700 --> 01:06:33,219 But at the same time he tried to understand my struggle at the time and then yeah. 526 01:06:33,220 --> 01:06:36,640 And, and even even Yeah. 527 01:06:36,640 --> 01:06:44,140 And the type of background a few and, and I told him why I wanted to leave the project at the time because it was that bad, 528 01:06:44,460 --> 01:06:52,150 it was really that but because the workload is, it's so is so much and, and the, 529 01:06:52,660 --> 01:06:59,670 the project, I mean we couldn't hire anymore just all the people that we have. 530 01:06:59,720 --> 01:07:03,460 And I have to do everything from the scratch by myself. 531 01:07:04,060 --> 01:07:09,850 That's really my struggle. I couldn't see the light at the end of the tunnel because the project is continuing. 532 01:07:09,850 --> 01:07:17,170 And I, I didn't see the, you know, the lifting, the finishing line of the project. 533 01:07:18,830 --> 01:07:22,010 Yeah, I, I said I couldn't, I couldn't handle it anymore. 534 01:07:22,010 --> 01:07:31,360 And this is, I think all this is I think I already given it all and I yeah, I think the the pressure was too much. 535 01:07:31,360 --> 01:07:35,740 Yes. Yes. I told them I want to I want to leave the project. 536 01:07:37,120 --> 01:07:43,990 And then he reminded me that, uh, this is what we are standing and working for. 537 01:07:44,020 --> 01:07:47,200 This is the time that we need to make use of our skills. 538 01:07:47,890 --> 01:07:56,350 And yeah, and if this vaccine is proven to be effective in the clinical trial, it will help a lot of people. 539 01:07:56,890 --> 01:08:06,820 And then he asked the question, mean, do you really want to stop now after all all of that we've done because I know he knows that I have quit this. 540 01:08:06,820 --> 01:08:10,060 Nobody else is going to do the the project is going to be stopped. 541 01:08:10,570 --> 01:08:18,190 And the point because in general, there there are no no other people except me in doing the process. 542 01:08:19,320 --> 01:08:29,980 And I was helped by my other people in different group but they don't know the whole lot of the process. 543 01:08:30,000 --> 01:08:33,100 Yeah, yeah, yeah. So what. 544 01:08:33,640 --> 01:08:40,640 But did he not say have a day off because he knows that he he knows that I know, 545 01:08:40,870 --> 01:08:49,290 I know that we couldn't really push anything back because the deadline they said I had to deliver the data by, 546 01:08:49,300 --> 01:08:53,260 by the experiment, I couldn't really feel anything. 547 01:08:53,740 --> 01:08:59,620 So thankfully all the next phone was running quite smoothly. 548 01:08:59,620 --> 01:09:03,489 So I didn't and this this no failed experiment. 549 01:09:03,490 --> 01:09:08,770 And it was just quite unusual for a scientific laboratory experiment. 550 01:09:08,770 --> 01:09:10,260 Very unusual. Yeah. And, 551 01:09:10,300 --> 01:09:19,000 and then the deadline they said and then we had like two or three meetings in the week which we have to give our data to our collaborator and the. 552 01:09:19,070 --> 01:09:20,840 Clinical trial data. Ready, set. 553 01:09:21,200 --> 01:09:31,700 So the first people got the injection during the second week are ending so they can delay the scheduled waiting for a second vaccination. 554 01:09:32,120 --> 01:09:33,950 The vaccine has to be produced. 555 01:09:35,030 --> 01:09:45,500 So so mixing up in this low, this manufacturing process, that means it'll be messing up the schedule of vaccination, which can help. 556 01:09:45,950 --> 01:09:50,900 But it was asking you. It was like asking you to hold the whole world on your shoulders. 557 01:09:51,740 --> 01:10:01,850 Yeah, that's right. That's why I was feeling the pressure and and what you told me a few times, even if you felt it's okay. 558 01:10:01,850 --> 01:10:06,920 Well, I know it's not okay because. Because, yeah. 559 01:10:07,190 --> 01:10:12,589 This nothing can be pushed back. Yeah, yeah, yeah. You know, it has to be done by a certain point and that's it. 560 01:10:12,590 --> 01:10:18,440 And then we don't have any leeway. There's no, uh, like this. 561 01:10:18,440 --> 01:10:22,589 No time to repeat the experiment. There's not time to analyse the data. 562 01:10:22,590 --> 01:10:31,069 I mean, the next day. So we get the data and the time, and then we have to analyse the data and then make the report and then send it to him. 563 01:10:31,070 --> 01:10:39,350 And he has to convey the message to everybody. So this not this, not even this line gap within the process. 564 01:10:39,950 --> 01:10:47,400 Oh, goodness me. I mean, I've talked to lots and lots of people and everybody's worked hard, but I don't think anyone's fault if you didn't. 565 01:10:49,270 --> 01:10:58,759 Uh, and I've got this question which I've asked everybody, but I think I already know what the answer is, which is? 566 01:10:58,760 --> 01:11:05,300 Do you think that the fact that you were able to work on something that affected everybody in the world 567 01:11:05,660 --> 01:11:12,950 and helped to support your own wellbeing at a time when the country was in this state of lockdown, 568 01:11:12,950 --> 01:11:20,810 was going on and everything was strange. I mean, did it did it help you psychologically to know that what you were doing was very important? 569 01:11:24,240 --> 01:11:30,960 At that point, I didn't I didn't feel the significance of my work at the point. 570 01:11:30,970 --> 01:11:34,150 I just I just. Oh, my my total. 571 01:11:34,150 --> 01:11:40,330 I just have to finish this work. And I people are still telling me that your work is important. 572 01:11:41,110 --> 01:11:46,090 But I don't feel I don't feel it because it's just like I'm doing my work. 573 01:11:46,420 --> 01:11:50,220 Yeah. Just like anybody. And they understand this. 574 01:11:50,310 --> 01:11:53,920 And so I think it was. It's more than that. 575 01:11:56,140 --> 01:12:07,719 So I think this is the final question. Has the experience of working on the on the project changed your attitude or your approach to your work? 576 01:12:07,720 --> 01:12:11,770 And, um, how would you like things to develop in the future for you? 577 01:12:12,460 --> 01:12:20,650 Yes. Yeah, I, I think it depends a lot of my perspective. 578 01:12:20,860 --> 01:12:26,079 I, I think, I think you should have noticed that I'm not very optimistic. 579 01:12:26,080 --> 01:12:33,340 So I think this, the first thing that I told my boss when she said, we need to do this by this time, I said, this is impossible. 580 01:12:33,340 --> 01:12:36,579 Yes, you know, I need this amount of time. 581 01:12:36,580 --> 01:12:42,370 I need me someone, more people. I need this amount of skills and we need this amount of budget money that we don't 582 01:12:42,370 --> 01:12:50,020 have any we don't have anything but some more use than like even even less so I mean, 583 01:12:50,410 --> 01:13:00,760 step by step. But, uh, yeah, I think, I think it's just a lot of one way approach from, from then that I think, 584 01:13:01,420 --> 01:13:06,970 I think from my logic thing by logic, maybe we should think and calculate everything logically. 585 01:13:07,330 --> 01:13:18,190 But for me we have just to deal with it first and do whatever you can do to accomplish your project. 586 01:13:18,820 --> 01:13:22,750 And then what if it goes in itself or it succeeds? 587 01:13:23,290 --> 01:13:38,259 At least you have done your best. And what I hope in the future is maybe I mean, is politically, if the there's more consideration to science, 588 01:13:38,260 --> 01:13:45,250 not only during the pandemic, but we should start investing in what we think is important for the future. 589 01:13:46,000 --> 01:13:50,530 So for science is not really a quick return. 590 01:13:50,710 --> 01:13:55,810 So we build all of the facts bit by bit, all the resources we can gather it. 591 01:13:56,200 --> 01:14:11,770 And then in the end, of course, we will find something useful for human aid and maybe for medicine, vaccines or whatever treatment it is. 592 01:14:11,950 --> 01:14:18,970 It's not built by, uh, short on short period of time. 593 01:14:19,750 --> 01:14:32,080 But if all this vaccine people have been working for years before I came to gender and then they tested and then they work on it for so long. 594 01:14:32,110 --> 01:14:38,049 And that's why we can quickly make something that can help a lot of human before. 595 01:14:38,050 --> 01:14:47,980 But, uh, without the support from government, no support from the industry and, and all from all of those years in the, in the past. 596 01:14:47,980 --> 01:14:58,000 Then we couldn't reach this point. Mm hmm. Yeah. I hope most people, more people will realise how important this science is. 597 01:14:58,610 --> 01:15:02,050 Yeah. For the application for human life. 598 01:15:02,410 --> 01:15:06,160 What about you personally? What, uh. What would you like to be doing in ten years time? 599 01:15:06,160 --> 01:15:09,550 Sorry, it sounds like it sounds like a job interview question with it. 600 01:15:10,150 --> 01:15:22,600 I mean, I, I, I like, I like science, I like working in the lab, but I would like to move towards leadership in the future. 601 01:15:22,830 --> 01:15:29,020 I'm, I'm impressed by the executive of that. 602 01:15:29,210 --> 01:15:30,820 People designed it. 603 01:15:30,820 --> 01:15:46,420 I mean, they accepted the, uh, the some, some certain condition from the firstly, like when we first collaborated with AstraZeneca also as if, 604 01:15:46,570 --> 01:15:51,520 when, if the vaccine had been approved, then it will be distributed with that profit. 605 01:15:52,330 --> 01:15:56,860 So those people in the executive board of AstraZeneca accepted that conditions. 606 01:15:57,520 --> 01:16:01,930 And then I think it's really noble of them to do that. 607 01:16:02,050 --> 01:16:13,180 I mean, instead of uh, instead of uh, but more important in the profit and put important in well-being of people. 608 01:16:13,450 --> 01:16:21,940 But I would like to be one of the yes, possibly in the future in a position to make that kind of decision making kind of decision that. 609 01:16:22,040 --> 01:16:26,809 Affects a lot of human life. Yeah. That's wonderful. 610 01:16:26,810 --> 01:16:31,310 Thank you very much. I'm. I'm very, very inspired. Thank you. 611 01:16:31,310 --> 01:16:31,957 I'm very, very.