Asia Regulatory Roundup: TGA orders re-evaluation of COVID-19 antibody studies amid false negative concerns

RoundupsRoundups | 19 May 2020 |  By 

Australia’s Therapeutic Goods Administration (TGA) has asked the sponsors of point-of-care tests for antibodies against the SARS-CoV-2 coronavirus to re-evaluate their clinical performance studies. TGA made the request after reviewing the findings of a postmarket evaluation carried out by a third party.
The Onsite and VivaDiag tests, which are made by CTK Biotech and VivaChek Biotech, respectively, came to market with instructions for use that quoted sensitivity figures claimed by their producers. Onsite’s claimed sensitivity was 96.86%. The claimed sensitivity of VivaDiag was 81.25% when used to analyze samples collected four to 10 days after the onset of symptoms, and 97.1% between days 11 and 24.
At the request of the Australian Department of Health, the Peter Doherty Institute for Infection and Immunity ran studies to verify the sensitivity and specificity data claimed by the manufacturers. The institute, a joint venture between the University of Melbourne and the Royal Melbourne Hospital, generated results that called the accuracy of the tests into question.
The Doherty Institute’s specificity results were two to four percentage points below the near-100% figures claimed by the manufacturers. That difference, while numerically small, could cause the tests to generate more false positives than true positives if a very small proportion of the population has antibodies against the virus.
Even so, TGA called the level of specificity seen in the Doherty Institute evaluations “adequate.” The agency is more concerned about the sensitivity findings. Across all samples tested by the institute, Onsite had a specificity of 56.9%. The figure increased to 84.8% in a subgroup of samples collected 20 days or more after the onset of symptoms but remained well below the claimed sensitivity. The VivaDiag data were similar, rising from 51.8% in all samples to 78.8% in the post-20-day subgroup.
TGA thinks the difference between the data generated by the manufacturers and Doherty Institute can partly be explained by “sample size and sampling bias.” The findings also confirm that serology tests are better suited to telling if someone has been infected with SARS-CoV-2 than making diagnoses during the acute phase of the illness. TGA is recommending serology tests only be used 14 days or more after the onset of symptoms.
In light of the Doherty Institute findings, TGA has asked the sponsors of the Onsite and VivaDiag tests to re-evaluate their own data, for example by stratifying the figures according to how long after the onset of symptoms the samples were taken. TGA thinks the re-evaluation will help it compare the data to the Doherty Institute findings and inform potential regulatory actions such as changes to the instructions for use and warnings about the limitations of the tests.
TGA, in collaboration with the Doherty Institute, is now reviewing the performance of another 30 serology point-of-care diagnostics to gain “a clearer understanding of the role these tests may play in the management of COVID-19.”
TGA Notice, More
Australia prepares for end of therapeutic good advertising pre-approval scheme
TGA has published advice for companies affected by the abolition of the advertising preapproval scheme. The question and answer document covers the rules that will apply to companies that want to advertise “designated therapeutic goods” in “specified media” from 1 July onward.
Until the end of June, manufacturers of complementary medicines and other designated therapeutic goods need to seek preapproval to run advertisements in print media, free-to-air television, radio and some other forums. That will change at the start of July, when Australia will move to a more self-regulatory regime. The change reflects the findings of the Review of Medicines and Medical Devices Regulation.
Ahead of the regulatory change, TGA has published advice to clear up potential points of confusion. The document explains that companies will not need approval to change advertisements after 1 July, even if the original version was approved under the old regime.
In the absence of preapproval, TGA is advising companies that are unsure if their ads comply with the regulations to “seek advice from a regulatory affairs consultant, a lawyer who specializes in therapeutic goods or engage the services of an independent vetting service.”
Companies that want preapproval can continue to use the outgoing process until 30 June. However, TGA said, “The utility of making an application will diminish as 30 June 2020 approaches and the application will lapse if no decision is made before 1 July 2020.” As the deadline nears, the group in charge of preapprovals will prioritize “high quality applications for compliant advertisements and other straight-forward decisions.”
TGA Notice, More
China’s CDE warns of phishing attacks targeting drug developers
China’s Center for Drug Evaluation (CDE) has warned drug developers of phishing attacks designed to steal information. CDE issued the warning as the scam tries to trick people into thinking they are using some of its systems.
The emails, which come from an address similar to that used by CDE, link to a website that mimics the Chinese clinical trial registration platform. By taking users to the fake platform, the scammers aim to install programs on their computers to facilitate the theft of their information. CDE does not know the source of the scam.
CDE is the latest in a series of regulatory agencies to warn of scams that play on their identities. The US Food and Drug Administration, for example, has issued alerts about fake warning letters and other scams that make use of its branding to extract information or money.
CDE Notice (Chinese)
Malaysia’s NPRA shares guidance on filing translated GMP documents
Malaysia’s National Pharmaceutical Regulatory Agency (NPRA) has issued guidance on submitting translations of official documents related to good manufacturing practices.
NPRA typically issues official documents in Malay, the national language of Malaysia. The documents may need translating to enable people outside Malaysia to understand them, for example when a national regulatory authority asks a company to submit official documents to support a request to import a product into its geographic jurisdiction.
To help companies in that situation, NPRA has identified three recognized translation bodies in the guidance. Translations that fail to meet a certain standard, such as those with “excessive” spelling and grammatical errors, may be rejected.
NPRA Guidance
TGA permits pharmacy-level substitution to counter metformin shortage
TGA has cleared pharmacists to counter the shortage of 500mg modified-release metformin products in Australia by dispensing other dosage forms containing the active ingredient.
With the supply disruption expected to last until 5 June or later, TGA has issued a serious shortage medicine substitution notice to ensure type 2 diabetics can continue to access metformin. The notice clears pharmacists to fill 500mg modified-release metformin scripts with 1000mg modified-release metformin or 500mg immediate-release metformin.
TGA is asking pharmacists to use their “professional and clinical judgement to determine whether a patient is suitable for substitution.” If a pharmacist substitutes a drug, TGA wants them to advise patients to check their blood glucose more often and let the prescriber now about the change as soon as possible after it is made.
Despite those stipulations, the substitution notice has raised concerns in some quarters. Gary Deed, chair of the Royal Australian College of General Practitioners’ specific interests diabetes network, criticized TGA’s handling of the situation, telling newsGP of a “concerning” lack of communication and failure to fully cover the risks of substitution in the instructions to pharmacists.
TGA Notice, newsGP


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy