Oh, what a tangled web we weave,
When first we practise to deceive!
— Marmion (1808) by Sir Walter Scott
It began with strategic incompetence. Prior to the early 1980s, there was no such thing as Big Pharma. Pharmaceutical companies were all big in those days, because that’s what it took to develop a safe, effective, fit-for-purpose medicinal product. In the same way, there is no Big Aerospace, Big Automotive, or Big Electronics sector of those industries; small fry can't make it. A company supplying highly complex products to consumer markets must be big to get all the research and design, manufacturing, and product distribution work done.
So, where did the boutique pharmaceutical trend that gave rise to Big Pharma come from?
In the early 1980s, pharmaceutical companies that had hitherto been highly vertically integrated began casting off their physical assets, including:
- Manufacturing facilities, making the people working in them redundant
- Distribution warehouses, making the people working in them redundant
- Quality control laboratories, making the people working in them redundant
- Clinical trials units, making the people working in them redundant
- Products that patients were dependent on (out-of-patent products that weren't making them cash any more)
Today, what are referred to as Big Pharma companies merely patent molecular compounds, hand them over to third-party contractors, and market the life out of the paltry few that are approved for sale. Those same Big Pharma companies have also outsourced drug development, to small companies that are no bigger than your local supermarket in terms of employee numbers—all in the name of reducing the risk of failure.
The small companies developing medicinal products (known as drugs in the US) will have never brought any kind of drug to market. How’s that for broken?
I explained the background to this strategic incompetence in one of my books, What Patients Need to Know About: Pharmaceutical Supply Chains. For this article, all you need to know is the outcome—pharmaceutical companies selling medicinal products are now dried-up prunes, compared to the fulsome plums they used to be.
Enter Lady Deceit
The number of new medicinal products coming to market every year has been in constant decline for many years. Jack Scannell et al. shone light on this in the paper Diagnosing the decline in pharmaceutical R&D efficiency, dubbing the trend Eroom's Law (Moore’s Law spelt backwards). They stated:
The past 60 years have seen huge advances in many of the scientific, technological, and managerial factors that should tend to raise the efficiency of commercial drug research and development (RD). Yet the number of new drugs approved per billion US dollars spent on RD has halved roughly every 9 years since 1950, falling around 80-fold in inflation-adjusted terms.
Even more tellingly, the US Government Accountability Office produced a report, dated November 2006, that confirmed this sorry state of affairs. Out of every 250 development candidates entering the development pipeline, just one gets approved for sale. Failure percentages for products in the industry were recorded as being in the high nineties. The report analysis also revealed the timelines in drug development:
- Preclinical studies = 3 years | Clinical studies = 7 years | Regulatory evaluation = 1½ years
- Total time to develop and gain approval = 11½ years (not the nine months of the Covid era!)
These shocking statistics have been hidden in the shadows, as patent protection allows pharmaceutical companies to charge eye-watering prices, enabled by massive sales and marketing budgets, keeping the customers rolling in.
The ugly truth is that this is an industry in deep trouble, trying desperately to keep its investors supplied with blockbuster returns, while staying tight-lipped on the worrying secrets within. I can confidently say that today, I’m revealing the truth.
Why so confident?
The reason I can say this so confidently is that I authored a book on the pharmaceutical industry, entitled Supply Chain Management in the Drug Industry: Delivering Patient Value for Pharmaceuticals and Biologics, which was published by specialist firm Wiley in 2011. It describes the above issues in detail.
The preface read:
I was staying at a budget hotel on the outskirts of London when I checked my Blackberry for email. It was probably around 3.00 a.m., so my sight was less than perfect. Squinting allowed me to make out the opening: “My name is Jonathan Rose, the Wiley editor for pharmaceutical science books.” Jonathan went on to say: “With interest, I note that you are leading the coming workshop ‘Supply Chain Management in Pharma/Biotech.’ Given the importance of managing supply chain procedures and costs during drug production and manufacture, I believe that a book explaining the concepts, methods, and applications of supply chain management to the pharmaceutical industry would make a timely and well-received text. Such a book would be an important reference and resource for professionals involved in drug development and manufacturing, quality assurance and control, chemical and biological engineering, and regulatory personnel.”
That is what I hope to have achieved with this book. I have attempted, of course, to contribute the maximum possible from my own personal databanks; along with this is supplementary commentary from what I can best describe as “expert witnesses.” The contributors have been hand-picked by me to reinforce, support, and move forward the sentiments in the book. Their powerful contributions are of varying length and depth.
I hope that you enjoy what we present here. The style is meant to entertain as well as to inform; and by informing, the hope is that the overall theme of the book strikes home—the pharmaceutical industry must change in radical ways if supply chains of the future are to meet stakeholder expectations.
I’ve included this short extract above to lend credibility to my comments and analysis here, so please excuse if it sounds immodest. It is, however, essential that as you read this article, you believe me, rather than lending unearned credence to the various actors involved.
Now for the greed and thirst for power
There was a tremendous amount of molecular patenting going on in the industry prior to 2009, delivering massive returns for investors of a more avaricious persuasion. There was no questioning of the goose’s ability to continue delivering its golden eggs. Numerous more cautious investors steered well clear of the peaks and troughs of this industry.
From 2009 onwards, the story takes on a far more complex form, as greed and thirst for power meld into each other, with governments beginning to play a leading role—none more so than the UK Government, under the sales pitch of a strategy for life sciences.
The first step was the creation of a British Office for Life Sciences. Wikipedia states:
The Office for Life Sciences was created in 2009 following an announcement by UK Prime Minister Gordon Brown on the establishment of a new cross-government unit to drive forward innovation within the healthcare system, and to support national policy making on the UK's attractiveness as a market for medicines and medical devices and technologies. The OLS was supported through its inception by Lord Drayson as Minister of State for Science and Innovation.
The OLS' first policy paper was entitled UK Life Sciences Strategy and was posted on the government website on 5 December 2011. The summary of key actions reads as follows:
We will take action to make the UK a world-leading place for life sciences investment:
- Early in 2012 the MHRA will bring forward for consultation proposals for a new ‘Early Access Scheme’ to increase the speed and efficiency of routes to market approval for innovative, breakthrough therapies.
- Through the MHRA, we will work with industry and other international regulators to develop actions which will create a more enabling regulatory environment for the adoption of innovative manufacturing technology. We will do this by the second quarter of 2012.
- We will invest £310m to support the discovery, development and commercialisation of research. This covers £130m for Stratified Medicine and £180m for a Biomedical Catalyst Fund.
- Through the NIHR, we will re-launch an enhanced web-based UK Clinical Trials Gateway in March 2012. This site will provide patients and the public with authoritative and accessible information about clinical trials in the UK.
- We will support patients to have access to novel treatments, and be part of the development of wider patient benefits by consulting on an amendment to the NHS Constitution so that, whilst protecting the right of an individual to opt out, there is a default assumption that:
- data collected as part of NHS care can be used for approved research, with appropriate protection for patient confidentiality; and
- patients are content to be approached about research studies for which they may be eligible, to enable them to decide whether they want a discussion about consenting to be involved.
- The Cambridge, Oxford and London BRCs will work with the BRU in Leicester, to develop a national NIHR Bioresource. This will make the UK the ‘go-to’ place for experimental medicine.
- As announced in the Autumn Statement 2011, we will introduce the EU VAT cost-sharing exemption in the Finance Bill 2012.
- We will hold a series of investment and policy events to promote the UK’s world-leading position in healthcare and life sciences in advance of the London 2012 Olympics.
- We will introduce, via Cogent, Higher-Level Apprenticeships (HLAs) covering post-A-level education. Our ambition is to deliver 420 Apprenticeships over the next five years.
- We will appoint two independent Life Sciences Champions: The first of these champions will act as chair of an independent Life Sciences Advisory Board. The second will act as a collaboration champion to foster partnership across the UK clusters and within government.
Note one of the comments that I have emphasised above: “This will make the UK the ‘go-to’ place for experimental medicine.”
An update is published soon afterwards
Hot on the heels of the initial strategy paper, an update was issued: the Life Sciences Strategy Update of August 2012.
Some key extracts from the letter:
The establishment of the Cell Therapy Catapult (previously known as the Technology Innovation Centre) is close to completion. To be based at Guy's and St Thomas' NHS Foundation Trust, London, and operational by this autumn, this centre aims to grow a UK-based cell therapy industry with access to finance, clinical and technical expertise to allow rapid exploitation of cell therapies.
Through the Medicines and Healthcare products Regulatory Agency (MHRA), progress has also been made in reducing the burden of regulation on research-active businesses, universities, and NHS trusts, ensuring that patients have access to promising, cost-effective new treatments.
We will continue to drive delivery, focusing on areas which you tell us are important and where we think we can do more. Our two Government-appointed life sciences Champions, Chris Brinsmead and Sir John Bell, are busy helping us do so.
These comments signalled a shift towards cell and gene therapies, regulatory ‘flexibility’, and advances in genetics.
Another strategy update after a mere twelve months
The Strategy for UK Life Sciences: One Year On morphed the Government's original British life sciences vision of just a couple of years previously into three rather different key principles:
- Building a life sciences ecosystem
We committed to build on our existing strengths and partnerships between universities, the wider research base, businesses, and the NHS to establish a cohesive system of integration.
- Attracting, developing, and rewarding the best talent
We acknowledged the need to nurture highly skilled researchers, clinicians, and technicians, assisting them to work collaboratively across traditional boundaries to create value throughout the ecosystem.
- Overcoming barriers and creating incentives for the promotion of health care innovation
We agreed to create the right environment to translate discovery into real benefits for patients and nurture innovation through the translational funding gap, whilst at the same time reducing regulatory bureaucracy to provide a route for early adoption and diffusion in the NHS.
Prime Minister David Cameron’s foreword included this passage:
Genetic science has the potential to transform healthcare systems around the world and support the emergence of British companies creating new jobs and revenues for the UK. My ambition is nothing less than for the UK to become the world leader in this emerging industrial sector, and this strategy document sets out the direction for how we will meet this global ambition. In the coming years, we will start to harness the power of genomic data in the UK to improve patient care, develop innovative new drugs and bioinformatics technologies, and create world-class genomic platforms for innovation that will drive global investment to the UK.
The world of life sciences is in a period of relentless disruption. Advances in technology are enabling new approaches to drug discovery, accelerating clinical development, and restructuring pharma supply chains. Innovative treatments such as mRNA vaccines and cell therapies are reshaping healthcare as we know it. But the thirst for investment in life sciences is endless and pharma is not immune to the impact of global economic turbulence.
My entry into implementation of the Office for Life Sciences strategy
In early 2013, I was contacted by the Technical Director of the UK's HealthTech and Medicines Knowledge Transfer Network (as it was then), now branded as Health KTN. He explained that no British life sciences company had been successful in bid submissions to the first two rounds of the UK's Advanced Manufacturing Supply Chain Initiative (AMSCI). He went on to say that the Office for Life Sciences was not happy with this. The feedback the OLS had received was that the bids were heavy on science but showed little understanding of the manufacturing supply chain. That was not a surprise to me!
Given my background, he asked whether I would be open to a four-day consultancy project to find a UK-based life sciences company that could fit the bill as a candidate to submit a bid for Round 3. The brief was to attend the launch meeting for Round 3 and 4, then to use my extensive network in biopharmaceutical supply chain strategy and management to identify a target company and sign them up.
I’ve never been one to turn down a challenge.
The launch meeting was held at the QEII Centre, the largest dedicated conference and exhibition space in central London.
The government description of this £120 million funding competition for manufacturing supply chain companies stated:
AMSCI is a funding competition designed to improve the global competitiveness of UK advanced manufacturing supply chains. £120 million is available for rounds 3 and 4, and the competition is open to all organisations that are part of a manufacturing supply chain. This funding is available to support research and development, skills training and capital investment. It will help UK supply chains achieve world-class standards and encourage major new suppliers to locate in the UK.
Michael Fallon said:
I cannot stress enough the importance of developing strong supply chains if we want major manufacturers to invest in this country. In the new rounds of AMSCI we will welcome applications from foreign investors who wish to establish or strengthen their manufacturing presence in the UK.
On the day at the QEII Centre, we were sat in tables of eight people around the room. Michael Fallon, one of a breed of politicians we no longer see (my opinion only), gave an excellent opening address. As the day progressed, people around the table began to chat, as they do. On our table, a gentleman representing a low-carbon vehicle developer, began to talk about the biotech industry.
Curious as ever, I asked him how he knew about this line of work.
“I’m the Chairman of Oxford Biomedica,” he revealed.
Well, you could have knocked me down with a feather duster.
More surprises were in store: the day ended with me being invited to visit the site to meet Oxford Biomedica’s Director of Manufacturing.
Next, it was a day at Oxford Biomedica’s facility in Cowley. It wasn’t difficult to find the site on the outskirts of Oxford. I had previously worked as a senior director at the site for two previous owners of the facility, British Biotech and OSI Pharmaceuticals. It overlooked the BMW manufacturing plant in Cowley, where we could watch the Minis rolling out, in various colours and shades, by the hundreds and thousands (not in work time, of course).
Oxford Biomedica (OXB) had purchased a biologics manufacturing facility on the site, known as Harrow House. OXB was then, and still is, a Contract Development and Manufacturing Organisation (CDMO), meaning that it provides scale-up solutions and commercial supply of viral vectors to pharmaceutical and biotech companies in the fast-growing field of cell and gene therapy.
The day went well, as the Manufacturing Director was not apprehensive of new ways of working. The next non-surprise was that the Head of Supply Chain had been a master production scheduler in my team at Bayer. I left with a commitment from OXB to draft a consultancy agreement for signature. Within a week, I was signed up.
As I always do, I began the assignment with a current state assessment. This involves mapping the inbound supply chain, the internal manufacturing flows, and the outbound journey to the next stage. The various items to be procured are identified, their suppliers listed, and data such as lead times and shipping conditions (mainly cold chain) are collected and documented.
Inside the plant, data on the stages in the process flow, batch sizes, production cycle times, waiting times, and a significant amount of other data were captured, and likewise for outbound flows. Now we had detailed the current state supply chain, it was time to work out the future state, or what was ‘to be’.
For this bid to be classed successfully as ‘an advanced manufacturing supply chain initiative’, it had to be something of exceptional merit, given that no other British life sciences company had achieved a successful bid to date. I was confident, however, because the company had good, skilled staff and the Director of Manufacturing was fully on board.
Knowing this was a gigantic challenge, I reached into my LinkedIn network (which, sadly, no longer exists) for a suitable ally. The right man whom I netted this way turned out be a Royal Academy of Engineering Professor at nearby Cranfield University—a former medic who, in another of these odd twists, had turned to designing Jaguar cars. This was the perfect candidate for an academic partnership on the project. He is still a very good friend today.
He put me in touch with a fellow Welsh person, who happened to be Head of Innovation at a hospital network in the English West Midlands: another perfect partner to provide the NHS perspective. She, likewise, is still a very good friend of mine.
Together, we were ready to work with OXB to deliver an end-user-focused model for developing gene therapy products—and the Office for Life Sciences (part of the Department for Business, Innovation and Skills (BIS) at the time) was delighted with the prospect.
How did it turn out? Cutting to the chase, the bid was successful and OXB received the funding sought:
Oxford, UK—11 September 2013: Oxford BioMedica plc (“Oxford BioMedica” or “the Company”) (LSE: OXB), the leading gene-based biopharmaceutical company, announces that it has been selected as a winner of a funding award under the UK Government’s Advanced Manufacturing Supply Chain Initiative (AMSCI), in recognition of the Company’s potential to become a world-leader in Advanced Therapy Medicinal Product (ATMP) manufacture and supply chain expertise.
Oxford Biomedica led the successful bid with four other UK-based participants: the Heart of England NHS Foundation, Cranfield University, Cell Therapy Catapult Ltd and Biotec Services International Ltd (together, the “consortium”). Subject to due diligence and final confirmation by Birmingham City Council, the consortium has been awarded a £2.4 million grant, of which Oxford Biomedica will receive £1.8 million, and a £5.3 million loan to Oxford Biomedica which is repayable by March 2017.
What followed was a get-together of the winning team with representatives from the Office for Life Sciences—some very clever young civil servants—and the fund administrators. Much patting of backs ensued.
My exit from the OLS strategy implementation
Not long after the project, I was asked to attend a meeting at the Business, Innovation and Skills Department's headquarters, chaired by a senior civil servant. The great and the good were there, representing Big Pharma, biotech, the OLS and other stakeholders in life sciences. Needless to say, my comments did not follow party lines, and that was the last such meeting I was to attend.
From then on, I became a disinterested keen observer of what was going on in cell and gene therapy and the broader life sciences landscape. I began to write articles that were widely published in industry journals, pointing out the gigantic logistics and supply chain management challenges presented by gene therapies—especially those known as autologous therapies, where the patient is both the source and destination of the product. As an example, I wrote Advanced Therapies: Patient-Centric Heaven or Supply Chain Hell?
My role as dispassionate observer persisted until the SARS–CoV–2 enigma struck. How could a biologically-derived gene therapy product be developed and manufactured in nine months?
That conundrum got me digging and digging, until the stark reality of what has gone on was laid bare.
The first bit of digging
Oxford Biomedica press releases revealed that the company had developed and manufactured the adenovirus drug substance for the AstraZeneca SARS–CoV–2 injections, as below, recounted chronologically:
8 April 2020
13 May 2020
20 July 2020
1 September 2020
6 October 2020
23 November 2020
30 December 2020
18 January 2021
1 July 2022
This public-domain chronology tells us that the AstraZeneca SARS–CoV–2 injections were developed, manufactured, and supplied at breakneck speed, and not by AstraZeneca or Oxford University. Remember, AstraZeneca has no capability to develop these products—and Oxford University certainly doesn’t.
It is the breakneck speed that is the real concern. How could the British regulator, the MHRA, award a Manufacturing and Import Licence (MIA)—which would have been required to undertake the development and manufacture—in the space of a few months, while only ever carrying out virtual inspections? That is just plain impossible, unless all the regulatory aspects had been totally ignored.
Further digging reveals dark forces operating
I found an article entitled Tough choices to reduce Ebola transmission, published in Nature on 13 November 2014. It speaks to the work that the Bill and Melinda Gates Foundation had been carrying out in Africa from the early 2000s, in the name of global health. If you scan through it, it could easily be applied to the Covid débâcle we have just been through.
Look at the team that created the article, with their job titles at the time:
- Christopher J. M. Whitty, chief scientific adviser at the UK Department for International Development.
- Jeremy Farrar, director of the Wellcome Trust in London, UK.
- Neil Ferguson, professor of mathematical biology at Imperial College London, UK.
- W. John Edmunds, professor of infectious-disease modelling at the London School of Hygiene & Tropical Medicine, UK.
- Peter Piot, director of the London School of Hygiene & Tropical Medicine, UK.
- Melissa Leach, director of the Institute for Development Studies in Brighton, UK.
- Sally C. Davies, chief medical officer and chief scientific adviser at the UK Department of Health.
You may recognise Whitty, Farrar, Ferguson and Davies (since knighted) as familiar names in the fearmongering campaign.
Prior to that article, Trevor Mundel, former global head of development with Novartis, joined the Bill and Melinda Gates Foundation as President, Global Health, in 2011. Mundel was recorded speaking at the Johns Hopkins University March 2014, under the title Global Health Needs Innovation. A more recent Gates Foundation interview with Mundel bore the title Developing COVID–19 therapeutics: An investment that needs to happen.
In it, he says:
Yes, there are comparable examples going back to the Second World War. Pharmas worked with governments to accelerate the identification and development of antibiotics based on Alexander Fleming’s initial discoveries from the late 1920s. This collaboration played a critical role in saving the lives of wounded soldiers.
That is twisting the truth, as he has missed out the fact that it took from 1928 to 1943 (fifteen years) to bring penicillin to the world. Was his omission to mention this salient detail an innocent mistake?
Then, Ian Hudson, CEO of MHRA, joined the Gates Foundation in 2019, as Senior Advisor, Integrated Development. His biography there states:
Dr. Ian Hudson has a leading role on the team in areas that include optimizing clinical studies and strengthening regulatory systems in Africa and other low-resource regions, particularly for malaria, polio, and COVID–19 drugs.
Ian was a practicing pediatrician before joining SmithKline Beecham in 1989 to work in research and development. In 2001, he joined the UK government’s Medicines & Healthcare products Regulatory Service (MHRA), where he served as director of licensing and then CEO. Ian was the UK delegate to the scientific committee of the European Medicines Agency’s Management Board, CHMP, later becoming its vice chair. He was also an honorary senior lecturer in clinical pharmacology at the University of London and served as chair of the International Coalition of Medicines Regulatory Authorities.
Hudson mysteriously set up a self-appointed organisation in 2016 (was he moonlighting?), which has the presumption to style itself the International Coalition of Medicines Regulatory Authorities (ICMRA).
The history of this outfit goes back to 2012:
In May 2012, before the 65th World Health Assembly in Geneva, more than 30 medicines regulatory authorities participated in a seminar promoted by Brazil aimed at stimulating a debate among health officials and the diplomatic community on how to improve cooperation among medicines regulatory authorities. The discussion highlighted the importance of better promoting and coordinating international cooperation among medicines regulatory authorities in order to strengthen dialogue, facilitate the wider exchange of reliable and comparable information, encourage greater leveraging of the resources/work products of other authorities, and promote better informed risk-based allocation of authorities’ resources. These efforts would strengthen the quality, safety and efficacy of medicinal products globally.
The irony is that the regulatory authorities (FDA, EMA, MHRA, Japan's PMDA, Brazil's ANVISA, Australia's TGA) were already fully harmonised. I was left with the distinct impression that ICMRA was nothing but the Trojan horse for the Gates Foundation to infiltrate and contaminate countries' regulatory bodies worldwide—with great success!
The current Chair of ICMRA is Ms Emer Cooke, also Executive Director of the European Medicines Agency. Make of that what you will.
UK Vaccine Taskforce steps in to fight SARS–CoV–2
Britain's Vaccine Taskforce was set up at the behest of Sir Patrick Vallance, chaired by Kate Bingham. The government press release stated:
Kate is temporarily stepping back from her full-time role as Managing Partner at SV Health Investors, a leading international life sciences venture capital firm to take on this role as Chair of the Taskforce.
Bingham reported directly to the Prime Minister.
The former CEO of Glaxo (now known as GSK) then took over the role, issuing an end-of-year report entitled UK Vaccine Taskforce 2020 Achievements and Future Strategy. The Vaccine Taskforce's objectives and the membership of its steering group are an instructive read.
The Government then transmogrified the objective by press release to: Bold new life sciences vision sets path for UK to build on pandemic response and deliver life-changing innovations to patients.
Now, the Taskforce is being absorbed into the UK Health Security Agency (UKHSA), headed up by Dame Jenny Harries, former Deputy Chief Medical Officer for England and a regular member of the Government’s daily news briefings on the rising SARS–CoV–2 infections that were supposedly set to kill millions. Those briefings preached lockdowns, masks and all the other measures that we know were diametrically opposite to what should have been done.
Then we have the Head of the Wellcome Trust, Sir Jeremy Farrar (whose role during Covid was equivalent to Dr Anthony Fauci's in the US). He is shortly to take up his post as Chief Scientist of the World Health Organisation. His book, Spike, proclaims:
My preference would be to streamline the architecture of global health with the WHO in the middle of the web, convening, advising, guiding and providing an emergency response [...] Crumbs from the table will not cut it in the era of pandemics.
Finally, we have Ian McCubbin (since knighted), the new Chair of the official British body charged with bringing truckloads of of mRNA products to the world—the flippantly-named Cell and Gene Therapy Catapult:
The Cell and Gene Therapy Catapult (CGT Catapult), an independent technology and innovation organisation, announces today the appointment of Ian McCubbin OBE, CBE, to its Board of Non-Executive Directors as Chairman, effective 1st February 2022. With over 30 years of experience in the pharmaceutical industry and as a pharmacist by training, Ian has worked for industry leading companies including GlaxoSmithKline (GSK).
A cursory perusal of the clinical trials database that the Catapult maintains reveals how little progress is being made.
The incestuous, opaque nature of this swirl of key players, companies, government departments, interests and objectives—coupled with an unhealthy partnership with self-admitted “enabling” regulatory bodies such as the MHRA—might lead the man on the street to suspect fraud on the public and the public purse.
Oh, what a tangled web of blind leading the blind
What you have just read is undeniably a tangled web. The actors in the web come in all shapes and sizes—high-net-worth individuals, NGOs, pharmaceutical companies, their suppliers, universities, research funding bodies, regulatory authorities, government agencies and, of course, government itself.
There is one thing they all have in common, however. That is, they lack expertise in how to develop, manufacture and distribute any kind of medicinal products—especially gene therapies, where they have been trying to solve the supply chain challenges for over a decade, with no meaningful success.
The author has been interviewed by TrialSite News about this article.