Asia-Pacific Roundup: TGA corrects misinformation about COVID-19 vaccine contamination

Australia’s Therapeutic Goods Administration (TGA) has responded to recent online reports that claim COVID-19 mRNA vaccines are contaminated with excessive levels of DNA.

TGA disputed the claim, calling it misinformation, in a statement detailing its issues with the reports. The agency said the reports are based on studies conducted by a few laboratories that have attempted to investigate the amount of DNA in COVID-19 vaccines. TGA found fault with the rigor of the studies.

The agency said the studies “fail to apply the required scientific rigor expected in pharmaceutical testing [and], as such, the results are not robust or reliable and are creating confusion and concern regarding the safety of vaccines.”

TGA divided its concerns into three parts. The first section covers selective reporting and method validation. TGA said some labs have reported DNA levels using a fluorometry test, “which is known to overestimate DNA levels in the presence of mRNA” because the fluorescent dye used in the test binds to both DNA and mRNA.

By effectively testing for both nucleic acids, the labs generate results that add the level of DNA, which may be present in minute amounts, to the known quantity of mRNA that must be in the vaccine for the product to work as intended. Existing guidance from the International Council for Harmonisation (ICH) notes the failure of fluorometry to meet the performance criteria required for DNA tests.

“The fluorometry method used in the quoted tests to measure residual DNA does not meet the requirement for specificity,” TGA said. “Specificity means the ability for the test to measure the substance of interest (in this case DNA) without measuring other similar substances (such as mRNA).”

TGA’s other issues with the studies relate to samples and the status of the labs. Some of the studies used as few as three samples, TGA said. Some of the samples were well past their use-by date or had already been opened and used, the agency said, and as such, were not suitable for testing. TGA is unsure where the samples were sourced and how they were handled before and during testing.

“Regulatory testing is conducted within tightly controlled frameworks to ensure that test samples cannot be manipulated and results can be relied upon. Processes that do not ensure traceability and certainty about the integrity and provenance of test samples impact the reliability of findings,” TGA said.

The final set of issues raised by TGA conveys the lack of evidence that the labs have good manufacturing practice certification, which is needed to perform approved testing for pharma companies or are accredited under the required ISO standard.

TGA also discussed the potential for residual DNA to cause harm. COVID-19 vaccines and other biotechnology products may have low, strictly controlled levels of residual DNA. While relatively new, mRNA vaccines have been safely used by billions of people, and the safety of other biotech products has been shown in millions of people across more than 40 years of use.

TGA Notice

India moves to strengthen pharmacopeial cooperation with seven countries

Indian officials have met with representatives from national regulatory authorities in Bhutan, Mauritius, Mozambique, Nepal, the Solomon Islands and Sri Lanka to discuss pharmacopeial cooperation. Officials from India and Fiji came together for another meeting about similar topics.

At the larger of the two meetings, the Indian Pharmacopoeia Commission (IPC) provided an overview of recent developments, such as the launch of its online portal and “growing international recognition” of its standards, with representatives from six countries. The goal was to strengthen pharmacopeial cooperation and establish an annual forum for ongoing collaboration.

Representatives of the six countries “shared their expectations, discussed mutual interests, and made various requests, such as additional subscriptions to the IP Online portal, training programs and access to reference standards,” IPC said.

At the meeting with Fijian representatives, IPC explained its role in setting pharmaceutical standards and recognizing the Indian Pharmacopoeia (IP) in parts of Latin America, Africa, and Asia-Pacific.

“Both sides discussed the benefits of IP recognition, including the availability of affordable drugs in Fiji, and addressed potential areas for collaboration, such as capacity-building and training programs,” IPC said.

The talks are part of a broader push to increase international recognition of the IP, which the Indian government has identified to clear barriers to drug exports. Afghanistan became the first country to recognize the IP in 2019; another 10 countries have recognized the standards since.

Press Release, More

TGA refuses to register Leqembi for Alzheimer’s

TGA has refused to register the Alzheimer’s disease drug Leqembi after concluding Eisai and Biogen have yet to show the benefits outweigh the risks. Eisai plans to ask TGA to reconsider its decision.

Regulators in countries including the US, Japan, China and Great Britain have approved Leqembi, but other regulators have concerns about the evidence. The European Medicines Agency (EMA) recommended refusing Eisai’s request for approval in July because “the observed effect of Leqembi on delaying cognitive decline does not counterbalance the risk of serious adverse events.”

TGA reached a similar conclusion last week. The agency said the clinical trial data showed people taking Leqembi experienced a reduction in disease progression compared to those on placebo. However, TGA deemed the reduction too small to provide a meaningful clinical benefit or to outweigh the safety risks.

The agency identified “the frequent occurrence of amyloid-related imaging abnormalities” as a safety concern. The abnormalities are a widely recognized risk of anti-amyloid beta antibodies but other global regulators have found the benefits of Leqembi outweigh the dangers.

Eisai said it will ask TGA to reconsider its position within 90 days. TGA will then have 60 days to deliver its final decision. Eisai also committed to seeking a re-examination of EMA’s opinion.

TGA Notice, Eisai Statement

TGA responds to questions on essential principles, clarifying effect on industry

TGA has published responses to questions asked as part of its public consultation on the use of essential principles in the regulation of medical devices in Australia.

The essential principles set out fundamental safety and performance requirements that devices need to comply with to be sold in Australia. In September, TGA gave a presentation on the proposed alignment of its essential principles with regulations in the European Union. The agency fielded questions at the event but ran out of time to answer them all. Last week, TGA published its responses to the questions.

TGA’s responses cover its plans to update the essential principles checklist, alignment with international initiatives such as the Medical Device Single Audit Program and the effect on manufacturers. The agency said it will help manufacturers to meet the requirements by establishing transition periods, guidance and compliance tools such as the essential principles checklist.

Officials are still finalizing the details of the transition arrangements but said, “we are not planning on requiring sponsors to tell us of their compliance to any amended essential principles.” Manufacturers will need to hold evidence of their compliance, though.

TGA Q&A

Asia-Pacific Roundup: TGA corrects misinformation about COVID-19 vaccine contamination

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