Ryan Mee, CEO of Fulcrum Metals, reviews FY23 and progress on the Gold Tailings Hub in Canada. Watch the video here.
AVA6000 is a therapeutic product based on proprietary pre|CISION™ technology which incorporates a substrate that is sensitive to cleavage by FAP. The pre|CISION™ substrate can be utilized in a drug conjugate linker or to generate chemotherapy prodrugs that are only activated in the tumor microenvironment. AVA6000 consists of a doxorubicin molecule covalently bonded to a dipeptide (pyridine-4-carbonyl)-D-Ala-L-Pro), which is designed to be susceptible to hydrolysis by Fibroblast Activation Protein a (FAP) but is resistant to hydrolysis by both closely related and wider mammalian peptidases. FAP, a post-prolyl endopeptidase, is overexpressed on the surface of activated fibroblastic cells which are abundant in the supporting stroma of over 90% of malignant epithelial cancers, as well as in bone and soft tissue sarcoma. While FAP is also present both in normal tissues and as a soluble enzyme in plasma, levels are significantly lower than those present in malignant epithelial cancers. Consequently, AVA6000 has the potential to deliver doxorubicin directly to the tumor microenvironment, while exposing the patient to a lesser degree of doxorubicin-associated toxicities. The primary mechanism of action of doxorubicin is thought to involve stabilisation of a topoisomerase-II-DNA cleavable complex through non-specific DNA-intercalation. The non-specific DNA-intercalation causes a number of downstream effects, which may ultimately result in apoptotic cell death. Although doxorubicin has been one of the most effective and widely used chemotherapeutic agents for the treatment of various solid malignancies for over 40 years, its clinical utility is limited by dose-limiting toxicities, including myelosuppression and cardiotoxicity. The unique FAP specificity of the N-(pyridine-4-carbonyl)-D-Ala-L-Pro leaving group conjugated to doxorubicin in AVA6000 is supported by the absence of cleavage of the fluorogenic analogue, 3114-AMC, in FAP gene-knockout mice (Fap-/-). In vitro cytotoxicity assessments involving human tumor cell lines showed that AVA6000 was between 80-fold to 4,000-fold less cytotoxic compared to doxorubicin. In several in vivo efficacy studies in tumours with high FAP levels, AVA6000 significantly decreased tumor volume and increased survival in a dose-dependent manner. In a PDX model of osteosarcoma, AVA6000 significantly decreased tumor volume while doxorubicin had no significant effect. The efficacy and tolerability profile of AVA6000 strongly support its clinical development, and a Phase I trial in patients with locally advanced or metastatic selected solid tumours cont....
https://www.oncodesign.com/wp-content/uploads/2022/01/AACR-2021_Avacta.pdf
With the move away from PCR, I don't understand why can't we present a case that's there is a need for a highly accurate LFT and get exceptional use. Other than they wont accept its accuracy, perhaps. We could at least try - MHRA claim we havent attempted it.
Dear *******,
The MHRA has not received applications for Exceptional Use Authorisations (EUAs) from Avacta PLC, Abingdon Health or Omega Diagnostics.
The UK Health Security Agency (UKHSA) has introduced the criteria for manufacturers seeking to place their tests on the market in the UK. This is known as COVID Testing Devices Authorisation (CTDA). All tests for COVID-19 must comply with the Medical Devices Regulations 2002 (as amended) and fulfil the requirements outlined in our guidance for industry and manufacturers of Covid-19 tests and testing kits.
In exceptional circumstances the MHRA can issue Exceptional Use Authorisations (EUAs) allowing medical devices to be used that have not followed the standard approval process. You can check the list of medical devices given exceptional use authorisations, which shows the list of manufacturers and their medical devices which have been granted an exemption by the MHRA during the Covid-19 pandemic. Surescreen Diagnostics is a manufacturer based in Great Britain and has received an Exceptional Use Authorisation for a self-test lateral flow device.
Dr Laura Squire, MHRA Chief Healthcare Quality and Access Officer, said:
“The MHRA recognizes the severity of the current Covid-19 pandemic and the importance of facilitating availability of tests.
“The EUA (Exceptional Use Authorisation) process has been used during the pandemic to ensure that the health system has access to critical products. Several manufactures and their medical devices have been granted an exemption by the MHRA, including manufacturers based in Great Britain.
“We only consider applications where there is a clear clinical need and there is no available supply of CE marked or already derogated alternatives. Potential applicants are encouraged to follow our guidance for manufacturers of Covid-19 tests seeking to apply for an Exceptional Use Authorisation.
“We will continue to work with partners to support the delivery of the government’s agenda on COVID-19 testing in order to support patient-centred care and access”.
Background:
The focus of the MHRA in considering any application is on the effectiveness and safety of the device. Exceptional Use Authorisations (EUAs) can be issued by the MHRA in exceptional circumstances, allowing medical devices to be used that have not followed the standard approval process.
Only the MHRA can issue an Exceptional Use Authorisation (EUA) for non CE-marked or non UKCA-marked tests. One of the requirements for the EUA application process is that the manufacturer is able to demonstrate there is a clinical need for the test.
The MHRA does not have a remit over which tests are purchased and deployed by the
"The question is which state will be shaping our world across the next decade, presenting big challenges for the UK, the answer is China." - Ken McCallum, head of MI5.
If we are to take MI5 seriously, to rely on lateral flow tests from China for the health of the nation's people and economy is at best insanity, at worse treachery.
Two years have passed since the arrival of Covid to these shores, it is a dereliction of duty not to have worked tirelessly to build a British diagnostics industry capable of supporting the needs of this country and ensuring the safety of the nation.
Who is responsible for this failing? They must be held accountable. Perhaps they should also be of interest to MI5 (do they have connections with China?)... over to you Neale Hanvey MP. Give them hell.
We have a duty to work towards 100% sovereign testing as soon as possible, we can't leave Britain dependent on China - it would be insane. Peto's comments are highly offensive and he should be removed from his role. Rather than deriding British manufacturers in the national press for 'whingeing', he should be supporting and assisting our diagnostics industry to produce tests that get approved.
It's the rough of a piece I've been working on. I've sent it to Wes Streeting to give him a shove. I just need to get a quote from Neale as opposed to a lift from Twitter, one from Medusa, then I'll file it to some media folk. That said, it could be all change tomorrow!
British companies have created the world’s most accurate lateral flow tests to stem the spread of Omicron but Government chiefs are refusing to allow them to be used.
There is currently a shortage of lateral flow devices in the country as the NHS awaits further shipments of cheap Chinese made tests - some of which are so poor it’s a 50/50 ‘flip of a coin’ whether they provide an accurate result.
Meanwhile scientists and manufacturers from the UK diagnostics industry - who have tested their devices against the latest variant and found them to be almost 100% accurate - are left facing financial disaster as the Tories backs China instead of Britain.
Neale Hanvey, MP for Kirkaldy and Cowdenbeath, worked for 25 years in the NHS has challenged the PM in the House of Commons to take action: “Can the Government please explain why they have pulled the plug on the UK diagnostics industry when additional capacity is so obviously required? It is beyond illogical."
Such is the mounting anger an online petition has been launched to call for an end to the low quality lateral flow devices from China in favour of supporting higher quality British made tests.
To date, the Conservatives have spent in excess of £3billion with Chinese manufacturers whilst UK tests remain in a Government backlog of medical devices awaiting the official rubber stamp for approval - red tape some of the Chinese products were given exemption for. During the first wave of the pandemic Britain was relying on tests so poor they had been banned from use in America.
UK testing companies such as Omega Diagnostics and Abingdon Health have seen their share prices tumble through Boris’ failings with both companies facing redundancies. In the early stages of Covid-19 Abingdon provided the Tories with over £5m of tests which so far the DHSC has failed to pay for. Other British diagnostic companies are also pursuing unpaid bills.
Avacta is the creator of what is believed to be the world’s most accurate Covid-19 test using revolutionary Affimers - the unique technology that sits inside the white testing cassettes and determines positive or negatives. The Yorkshire-based company has teamed up with Boohoo retail boss and billionaire Mahmud Kamani to manufacture up to 30 million tests per month under the MeduFlow trademark - pinpoint accurate LFTs which could effectively render expensive and slow PCR testing redundant.
Kamani’s MeduFlow has CE marking for home use in the UK but also requires a new Covid Testing Device Authorisation (CTDA). However, the Govt is currently sitting on its hands refusing to issue the paperwork and order MeduFlow preferring to wait for cheap Chinese imports as the country faces an LFT drought - an issue Labour described as ‘a total shambles’.
This from MHRA. I've no idea why we never applied for Exceptional Use when others clearly did.
Dear XXXX,
The MHRA has not received applications for Exceptional Use Authorisations (EUAs) from Avacta PLC, Abingdon Health or Omega Diagnostics.
The UK Health Security Agency (UKHSA) has introduced the criteria for manufacturers seeking to place their tests on the market in the UK. This is known as COVID Testing Devices Authorisation (CTDA). All tests for COVID-19 must comply with the Medical Devices Regulations 2002 (as amended) and fulfil the requirements outlined in our guidance for industry and manufacturers of Covid-19 tests and testing kits.
In exceptional circumstances the MHRA can issue Exceptional Use Authorisations (EUAs) allowing medical devices to be used that have not followed the standard approval process. You can check the list of medical devices given exceptional use authorisations, which shows the list of manufacturers and their medical devices which have been granted an exemption by the MHRA during the Covid-19 pandemic. Surescreen Diagnostics is a manufacturer based in Great Britain and has received an Exceptional Use Authorisation for a self-test lateral flow device.