Journey

Senator Malcolm Roberts:
Dr. James Rowe is a pharmaceutical scientist with over 40 years of experience in the pharmaceutical industry and academia in the design, development, and testing of novel drug dosage forms. He has held academic positions at the University of London, the University of Sydney, and Western Sydney University. His research interests are in pharmaceutics and pharmaceutical chemistry. In the pharmaceutical industry, he has worked in drug formulation and production for multinational pharmaceutical companies, including Lilly, Bristol Myers Squibb, and 3M laboratories in Australia and in the UK. He’s the author of several patents relating to the formulation of novel drug dosage forms.

Dr. Rowe is a graduate in pharmacy from the University of Sydney, and holds a Masters of Science and Ph.D. degrees for the University of London in biopharmaceuticals and pharmacokinetics. He has appeared as an expert witness on over 30 occasions in many jurisdictions, including the USA, Australia, New Zealand, and Canada on intellectual property matters relating to patents on drug formulation and pharmaceutical production. In 2015, Dr. Rowe was elected a fellow of the Royal Society of New South Wales for his contributions to intellectual life in New South Wales, particularly in the pharmaceutical industry in matters relating to drug dosage, form, design and analytical chemistry.

Dr. Rowe is going to discuss for us the manufacturing of vaccines and the variations of vaccines. He’s on a tight schedule. We’ve got no pictures, so we’ll just have to listen to you. Dr. Rowe, over to you. Thank you so much for appearing.

Dr James Rowe:
Thank you. Can you hear now?

Speaker 3:
Yes, we can.

Dr James Rowe:
Good afternoon, ladies and gentlemen. It’s relevant how I first became involved in this particular matter. It’s what I mentioned to a colleague, Dr. Altman, who has presented here this morning. I asked him why ivermectin and hydroxychloroquine were not recommended as the first line treatment for COVID infections. I say this because I’ve done several formulations of ivermectin in the past, during my normal course of work, and I was well aware of its activity and its antiviral activity. As a consequence, I followed the literature on it and I have in front of me several papers, which show its safety and efficacy in the treatment of COVID-19. In fact, I have a meta study on 61 studies testifying to that event.

Subsequent to that, I was given lots of information from Dr. Altman and Mr. Julian Gillespie concerning the safety and efficacy of the vaccine, which has raised some alarming issues to me. I understand most of the information provided to me has come from the EMA, the European Medicines Agency, the emails, freedom of information requests, and Pfizer court order documents. The opinions I express are based on the assumptions of these documents are authentic.

What I’d like to talk about is the differences in the batches of the COVID- 19 vaccines. Around about in the latter part of 2020, the European Medical Agency expressed concern about the difference between the percentage mRNA integrity in the clinical batches, and those of the proposed commercial batches. In the clinical batches, around 78% of the mRNA was encapsulated. In the proposed commercial batches, only 55% of mRNA was encapsulated. The reason for the low integrity observed with the commercial batches was not identified.

Now, just to explain, you might well imagine that when you’re doing a small clinical batch or a trial batch, the equipment used and the manufacturing process may be quite different to the manufacturing process and the equipment you use in larger commercial batches. For instance, the filtration system, the mechanism of stirring, etc.

Now, the EMA expressed concern of this, but there was no identification of why there was any difference. As far as I’m aware, there’s been no studies done on what happened to the rest of the RNA. Now, this could be very important because the rest of the RNA is inactive, and therefore, it may well result in some type of side effects. It may be a degradation product. And then, again, it may code for different types of proteins, which may be toxic.

I say that there was no work done, because it was of only a few weeks after the EMA, the date of the EMA emails, that the provisional approval was given the go ahead. So, how was the percentage of RNA finally solved? My information was that it wasn’t solved at all. From the documents I see, what actually happened was that the specifications for the percentage integrity of the mRNA was actually reduced to a minimum of 50%. So, what in fact happens was the specifications were changed to fix the problem.

I’ve mentioned this, what has happened to the rest of the RNA? I don’t know. So, it could be argued that no clinical or stability testing was performed on the batch formulation, which was used in the commercial manufacture of the vaccines. We also have clinical evidence that supports the batches being somewhat different. I’ve seen the table which compared the incidence of side effects associated with each batch number in each state of the United States. If all the batches were the same, one would expect the side effects to be randomly distributed. However, the data shows that the side effects are not randomly distributed.

More than 80% of the batches only have one or two side effects, so they can be generally regarded as safe, while some of the others have side effects over a thousand times that of the other batches. These side effects include hospitalisation, even death, and this was experienced in every single state of the USA. So, it can’t be due to some sort of demographic change from one state to the other. This suggests, as I’ve said, that the only one reason as far as I can see is that the batches were different. There are some batches which are in fact extremely toxic, and there are some which are quite safe.

Now, you might say, well, what is the reason for the differences? Well, we don’t know. Just the same as we don’t know what the explanation was for the differences in the potency in the clinical batches versus the commercial batches. But there may be several reasons for why there is a difference.

Firstly, there doesn’t appear to be any scale up done from the clinical trial batches to the commercial batches. When I say scale up, I mean that if you are making a very small batch, as I said before, you’re using different equipment, maybe different filtration system, maybe lots of different things. Even the degree of agitation, which can affect the integrity or the tertiary structure of proteins.

The TGA, FDA, and the ICH also issued guidelines for the scaling up process. I don’t see any of this actually being produced.

What I’d like to read to you is one small chapter in the guidelines which talks about manufacturing variations and stability data for scaled up batches. It basically says, “Any change in the manufacturing process has the potential to impact the quality of the active substance and/or the drug product. Therefore, the impact of the change on quality characteristics and stability has to be assessed, because these are integral changes to the overall assessment of comparability of biological medicines before and after changes are made to the manufacturing process.”

The guidelines then go on to say what you should do and all the processes that are involved in the scaling up of the manufacturing process. The other thing that may be different is the actual percentage of encapsulation of the RNA into the microparticle itself. The microparticle basically consists of a core of mRNA, which is coated by various lipids. I’ve actually had a lot of experience in this.

In fact, many years ago, my Ph.D. was involved in microencapsulation of drug products. Let me tell you, small changes in the manufacturing process, such as the change in the core to coat ratio, in other words, the amount of the coat compared to that of the core, slight changes will affect the degree of encapsulation, the temperature, the extent of stirring, etc. makes a huge difference. I don’t see any of that being validated. So, that might be a significant reason why there is a difference. That’s pure speculation on my behalf.

What I can say is the differences in the manufacture, one involved the two-step process rather than one, it was produced on a different scale, and also was produced in a different manufacturing facility. From the information I’ve received, it appears that the standard procedures is a scaling up on validation of the overall manufacturing process was not followed, and as a likely explanation for the variability in the batches.

So, we have different clinical proof that there is differences in the batches, and we have chemical proof as well as shown in the EMA emails. That concludes my presentation.

Senator Malcolm Roberts:
Thank you very much, Dr. Rowe. Just someone, Christine Dolan, who was a witness just before you said that the batches are different because pharma blew off testing. In Pfizer, at every manufacturing step, they neglected to test at every step. We know that in the United States, because it’s in the Pfizer documents. Does that make sense to you?

Dr James Rowe:
Yes. That makes perfect sense to me.

Senator Malcolm Roberts:
Does anyone here have any questions?

Craig Kelly:
Dr. Rowe, is there any evidence about the different batches in Australia with the different rates of adverse events like there is in America? Is that only in America?

Dr James Rowe:
I’m sorry. The sound is extremely bad. Could you repeat that?

Craig Kelly:
I’ll just jump in. Is there any evidence in Australia, like there is in the States, about different batches having different rates of adverse events?

Dr James Rowe:
I have not seen that. The data from the US came from the official database, and I understand that data has been verified. I’ve not seen anything similar in Australia.

Senator Malcolm Roberts:
So really, we’ve seen, even in food production, this would’ve been a very serious offence, but this is now medication. It’s just disgrace for what’s going on.

Dr James Rowe:
Well, yes, the medications… It’s been obvious to me that the medication varies from batch to batch. Also, we have seen in some batches, the appearance of small nanoparticles, which are probably the result of the coating materials which hasn’t encapsulated the drug. We’ve actually seen that in several batches.

Senator Malcolm Roberts:
In other words, the testing of the original formulation, if that’s the word they use, does not apply to the actual manufactured products.

Dr James Rowe:
Absolutely correct.

Senator Malcolm Roberts:
We know that the testing for the original formulations that were put through trials, scanned as they were, they weren’t anywhere nearly fully tested at all, but even those shotty results don’t apply to the manufacturer. So, we’ve basically got an untested product, completely untested product.

Dr James Rowe:
That’s exactly what I’m putting forward. I’m saying that it could be well argued that no clinical or stability testing was performed on the formulation, which was used in the commercial manufacturer of the vaccines.

Senator Malcolm Roberts:
Thank you very much, Dr. Rowe. We’re going to end it there. I thank you so much for bringing your expertise, more than 40 years in big pharma, including manufacturing and testing. Thank you so much for contributing.

Dr James Rowe:
Thank you.