Out of control - Innova lateral flow test - Scott Farnsworth Intellectual Property

Introduction

Project Moonshot was the government’s polymerase chain reaction (PCR) mass testing programme for SARS-CoV-2, intended to administer 10 million tests per day by the early part of 2021 and with a whopping budget of £100 billion. Unknown to many, Project Moonshot per se was shelved less than 4 weeks of its announcement [1] following the threat of legal action by the Good Law Project claiming the programme was unlawful as it ignored scientific evidence and committed a vast sum of public money with no transparency over decision making. [2] Quietly, Project Moonshot became part of the NHS Test and Trace scheme: gone and forgotten. [3]

Innova Medical Group Inc

Bent upon the idea of mass testing, the government turned its attention to a different testing strategy and went on to spend and commit to spend eye-watering sums of public money in order to purchase huge numbers of SARS-CoV-2 antigen rapid qualitative test kits, commonly known as lateral flow tests (LFTs). These LFTs were purchased and continue to be purchased from a newly formed start-up, founded on 20 March 2020, called Innova Medical Group Inc (Innova), a US corporation wholly owned by Los Angeles based private equity house Pasaca Capital. [4] Pasaca Capital was founded in 2017 by Chinese-born billionaire Dr Charles Huang (PhD in marketing), who was born and studied in Wuhan: small world.

Introducing LFTs

In charge of the new unprecedented mass screening programme was the head of NHS Test and Trace, Baroness (Dido) Harding. It was under the backing of Baroness Harding that the assessment of LFTs was carried out by Public Health England’s Porton Down laboratory and Oxford University, for the purpose of evaluating LFT specificity and sensitivity. Specificity (true negative rate) is the ability of a test to correctly identify people without the disease: the person does not have the disease and the test is negative, whereas sensitivity (true positive rate) is the ability of a test to correctly identify people with the disease: the person has the disease and the test is positive. The preliminary report (the Report) was published on 8 November 2020.

The Innova LFT

Over 130 suppliers of LFTs were identified by the DHSC for desktop review, 40 of which were sufficiently promising and referred to Porton Down for evaluation. According to the Report, the Innova LFT, the test that had been used in a Liverpool pilot scheme, was the most advanced in stages of validation and nearing completion. The Report summarised its performance characteristics: a test specificity recorded as 99.68%; an overall false positive rate of 0.32%, and an overall sensitivity of 76.8% for all PCR-positive individuals – over 95% of individuals with high viral loads – and showing a minimal difference between the ability of the test to pick up viral antigens in symptomatic and asymptomatic individuals.

The Innova LFT was the only test to have been part of the pilot scheme and was different to other LFTs in the rapidity of its results. Working in a similar way to a pregnancy-style test, a result could be delivered between 15 and 30 minutes. The Innova LFT was also portable, much cheaper than the PCR test, did not need to be processed in a laboratory, and could detect the virus directly without the amplification steps of the RT-PCR test.

Red flags

In fact, sensitivity of the Innova LFT was optimal only when used by laboratory scientists at Porton Down (156/197 positive [79.2%, 95% CI: 72.8-84.6%])]. Sensitivity fell when used by fully trained research healthcare workers (92/126 positive [73.0%, 95% CI: 64.3-80.5%]) and fell dramatically still when used by self-trained members of the public given a protocol (214/372 positive [57.5%, 95% CI:52.3-62.6%]; p<0.0001 chi2(2)=30.1. The far lower rate was not flagged as a problem, notwithstanding the Report’s concession that delivery of appropriate training appeared important to test performance. [5]

Necessarily, it was the government’s intention that Innova LFTs would be used for self-administration by members of the public. It is a reasonable assumption that training in the use of LFTs (if any) would be minimal and random and test performance lower than the 57.5% stated in the Report. In fact, such lower performance was evidenced in real world data taken from the pilot scheme and produced by scientists from Liverpool University. In the pilot scheme, Innova LFTs detected only 48.89% of SARS-CoV-2 infections in asymptomatic people, when compared with a PCR test and failed to detect 3 in 10 cases with the highest viral loads. [6]

Within days of the Report, experts warned that Innova LFTs may miss as many as half of COVID-19 cases. [7] Jon Deeks, professor of biostatistics at the University of Birmingham, highlighted concerns over figures for self-administration by members of the public. The Report stated the test’s sensitivity was 58% [sic. 57.5%], when used by the public and that the false positive rate was 0.38% (0.16% to 0.88%). While 0.4% (400 in 100,000) was a very low rate, with a sensitivity of 58% [sic. 57.5%] and specificity of 99.6%, this would mean that 100,000 people being tested would find 630 positives, of which only 230 would actually have COVID-19, while 400 would be false positives.

The poor detection rate of Innova LFTs made it entirely unsuitable for the government’s proclamation at the time that it would allow the safe test and release of people from lockdown and students from university in the lead up to Christmas 2020, as the tests may miss up to half of COVID19 cases, and although a negative test result indicated a reduced risk of infection, it did not exclude COVID-19. Independent evaluations for the WHO had shown other LFTs likely to outperform Innova and even those did not have high enough sensitivity to rule out the SARS-CoV-2 virus.

Other research [8] claimed Innova LFTs were highly inaccurate, when early results from students testing at the University of Birmingham and universities in Scotland showed tests had a sensitivity of just 3% and that 58% of positive test results were false.

Birmingham spent six days testing 7,500 students with Innova LFTs in a process overseen by Alan McNally, director of the university’s Institute of Microbiology and Infection, who in March 2021 was seconded to set up the first flagship COVID-19 testing facility in Milton Keynes. The team found 2 positives in 7,189 students, which scaled up to 30 per 100 000 and was shocking in itself, as the city of Birmingham, in fact, had a rate of 250 cases per 100,000. The team retested 10% of samples that had been negative with Innova LFTs and found 6 false negative cases, raising the rate to 60 per 100,000.

Scottish universities conducted a total of 43,925 LFTs. Of those, 79 (0.2%) were positive, although a preliminary analysis of 31 of the positive samples showed that only 13 were, in fact, positive on PCR testing, giving a false positive rate of 58%.

Warning signs

On 10 June 2021, the US Food & Drug Administration (FDA) warned the public to stop using Innova LFTs. The FDA stated its significant concerns that the performance of Innova LFTs had not been adequately established, presenting a risk to health. In addition, labelling distributed with certain configurations of the test included performance claims that did not accurately reflect the performance estimates observed during clinical studies of the tests. Recommendations of the FDA warned the public to either destroy the tests by placing them in the trash or return them to Innova.

In fact, limitations of Innova LFTs had been acknowledged in the manufacturer’s original instructions for use (the Instructions). The Instructions made it clear the test was for:

the qualitative detection of nucleocapsid antigens from SARS-CoV-2 in human nasal swabs or throat swabs from individuals, who were suspected of COVID-19 by their healthcare provider within the first five days of the onset of symptoms, meaning it was not designed to screen the asymptomatic; and
use by clinical laboratory personnel and individuals similarly trained in point of care settings, meaning it was not designed for self-administration by members of the public.

Alarmingly and notwithstanding the Instructions, Innova LFTs were repackaged for the NHS with a different version of the Instructions as of 24 November 2020, which stated ‘You can use this self-test kit if you have symptoms or if you are asymptomatic (you do not have symptoms).’ The NHS version of the Instructions were hastily updated on 16 January 2021 with the removal of the referenced sentence.

Costing the earth

Confidence in the efficacy of Innova LFTs pre-dated and postdated their clinical evaluation and by some months. Examination of the government’s purchase contracts for Innova LFTs has shown Innova’s first contract was agreed as early as September 2020 and before PHE and Oxford University had published results of their evaluation. On 11 November 2020, in response to the Report, Sir John Bell, Regius Professor of Medicine at Oxford University, described the Innova LFTs as inexpensive. To date, government contracts for Innova LFTs total in excess of £3.3 billion: [9]

on 17 September 2020, details of a first contract were published with a contract price of £103 million (∑£103 million);
on 6 November 2020 details of a second contract were published with a contract price of £496 million (∑£599 million);
on 18 December 2020, a modification notice was published indicating an increase of the first contract price to £226 million (∑£722 million);
on 9 February 2021, a modification notice was published indicating an increase of the second contract price to £722 million (∑£948 million);
on 19 March 2021, details of a third contract were published with a contract price of £912 million (∑£1,860 million); [10]
on 23 March 2021, a modification notice was published indicating a second increase of the second contract price to £875 million (∑£2,013 million);
on 20 May 2021, details of a fourth contract were published with a contract price of £1,200 million (∑£3,213 million);
and on 15 July 2021, details of a fifth contract were published with a contract price of £144 million (∑£3,357 million).

Made in China

Disregarding the FDA’s safety concerns, on 17 June 2021, the MHRA announced that it was extending the UK’s emergency use authorisation (EUA) for Innova LFTs through to 28 August 2021. Graeme Tunbridge, the MHRA Director of Devices, stated in the announcement that a full risk assessment had been undertaken by the DHSC as legal manufacturer of [Innova LFTs] in the UK. According to law, one device may have multiple legal manufacturers and each may have regulatory responsibility for that device. Innova LFTs are ‘Manufactured for the NHS’ and their labelling makes this clear. As the DHSC buys finished LFTs from Innova and relabels them with NHS branding, the DHSC is considered the legal manufacturer. In fact, Innova LFTs are made by Innova’s primary contract manufacturer, Xiamen Biotime Biotechnology Co Ltd, based in Fujian, China, and by 31 August 2021, the government had spent in excess of £100 million transporting Innova LFTs from China.

Innova claims to be investing in a facility in Rhymney, South Wales, as part of a collaboration with Sharp Packaging, a division of Healthcare PLC, to make Innova LFTs within the UK. Production was expected to begin in early July 2021. A request from this author to Sharp Packaging for an update upon the production schedule was declined for reasons of confidentiality. The DHSC will continue responsibility for Innova LFTs as the legal manufacturer, as Innova and Sharp Packaging go to lengths to talk of their collaboration to manufacture Innova LFTs over the next 3 to 4 years. Meanwhile, Innova’s EUA has expired, suggesting more government contracts for Innova LFTs lay on the horizon, or why begin the collaboration at all?

Conclusion

There is an overwhelming sense of government undermining superior domestic diagnostic tests, while propping up discredited Chinese imports. Of the total £4.5 billion spent by the government purchasing LFTs so far, 74% (£3,357 million) has gone to Innova alone. Such spending has led to widespread concern the UK is too reliant upon Chinese-manufactured imports, rather than investing in its domestic manufacturing capacity and raised the risk of shortages: so much for a greater economic autonomy post-Brexit. To exacerbate the undermining in domestic manufacturing capacity, it was reported in June 2021 that Lord Bethell (DHSC minister) had contacted members of the UK Rapid Antigen Test Consortium, a coalition of industry scientists and manufacturers, who had come together to secure LFTs and manufacturing capability for the UK, telling the members the government would draw the consortium’s efforts to a close. [11]

This article was originally featured in Lex Scientia edition two. Sign-up to receive the e-magazine directly to your inbox.

[1] The project was announced at a Downing Street briefing led by Boris Johnson on the 9 September 2020 and abandoned by the 6 October 2020.

[2] Government lawyers responded to the claim that Project Moonshot was designed to provoke discussion: it did not reflect an adopted policy, and there had been no decision to approve and commit £100 billion of public money to Project Moonshot. Indeed, no financial commitment had been entered into approaching anything like that sum.

[3] PCR testing was reintroduced in January 2021, under the NHS Test and Trace programme, as confirmatory tests for positive results taken from LFTs. TheNHS Test and Trace programme had its own approved ‘core’ budget of approximately £12.1 billion.

[4] Innova and Pasaca Capital act, in effect, as one. The head office address for Innova is the same as that for Pasaca Capital. The board of Innova is the same as that of Pasaca Capital.

[5] The Phase 3b evaluation (with laboratory scientists and fully trained research healthcare workers) involved throat swabs placed directly into the kit buffer solution rather than using a viral transport medium.

[6] BMJ2020;371:m4848.

[7] BMJ2020;371:m4469.

[8] BMJ2020;371:m4941.

[9] Source: https://bidstats.uk/tenders/?q=innova#757268479-737214508-70

[10] The contract was a 5 supplier agreement including Innova, Una Health, Siemens Healthcare Diagnostics, Tanner Pharma, and Abbott Rapid Diagnostics.

Out of control – Innova lateral flow test