Asia-Pacific Roundup: TGA updates analytical, clinical performance requirements for seasonal influenza tests

| 31 May 2022 | By Nick Paul Taylor 

Australia’s Therapeutic Goods Administration (TGA) has updated its guidance on clinical performance requirements and risk mitigation strategies for seasonal influenza rapid antigen self-tests and combination tests. The second iteration of the guidance features more detailed analytical and clinical performance requirements.
TGA published the original guidance document in March 2021 to help manufacturers benefit from the change in the regulation of self-tests that happened the previous year. Australia banned self-tests for serious diseases in 2010 but softened its position over the following decade, allowing the use of HIV self-tests in 2014 and lifting the ban on self-tests for diseases including seasonal influenza in 2020. The guidance describes risks developers of influenza self-tests must mitigate and conditions they must meet.
In updating the guidance, TGA has focused on the evidence required to both demonstrate the analytical performance characteristics and support the clinical performance of seasonal influenza tests. The section on analytical requirements lists the studies that applicants should include in their technical files when submitting their paperwork to get tests added to the Australian Register of Therapeutic Goods.
TGA expects applicants to submit data from studies of sample stability, analytical sensitivity, reactivity and specificity, precision, high dose hook effect, validation of internal control and external requirements. The guidance provides details of each study, explaining, for example, that manufacturers should run analytical reactivity studies using inactivated virus for at least 10 strains for influenza A, including H1N1 and H3N2, and five influenza B strains. The selected strains should be relevant to Australian settings.
The section on clinical requirements explains that a study “must be performed that best simulates a clinical setting,” adding that published journal articles cannot be used as evidence and contrived samples are not acceptable in determining clinical sensitivity and specificity. TGA wants manufacturers to clearly identify if their tests are limited to the detection of symptomatic influenza or can also be used to detect the virus in asymptomatic individuals.
A subsection on symptomatic testing is the largest part of the clinical requirements section. In the subsection, TGA states all claimed sample types, such as nasal swabs, must undergo clinical evaluation. TGA goes on to explain that it expects “statistically relevant specimen numbers and sample selection appropriate to each strain of influenza detected for the evaluation of an influenza rapid antigen test” and to provide further details of what is expected of manufacturers.
“Clinical sensitivity and specificity claims must include confidence intervals that reliably meet the minimum required level of performance,” the guidance states. “Positive samples are expected to be characterized (e.g. description of patient symptoms; day of collection post symptom onset; RT-PCR crossing threshold (Ct) values) and discordant results investigated using testing algorithms in accordance with a well-established laboratory case definition for influenza.”
The guidance features shorter subsections on asymptomatic testing, usability studies, user comprehension, inter-reader variability, invalid test rate and user sensitivity and specificity studies. The section on asymptomatic individuals states that rapid antigen tests generally have “markedly reduced clinical performance” in people without symptoms and manufacturers need to “include a substantial number of both symptomatic and asymptomatic individuals” in their studies to show clinical efficacy.
TGA Guidance
Philippine FDA seeks feedback on automating license to operate application processes
The Philippine Food and Drug Administration (FDA) is holding a consultation on plans to “reengineer and streamline” its process and automate its system for initial, renewal and variation license to operate (LTO) applications through its electronic system.
FDA’s draft guidance applies to manufacturers, clinical research organizations, sponsors and other organizations that work with products including drugs and need to obtain an LTO to operate. The draft begins with general guidelines, explaining that establishments need a qualified person and must comply with good practices before describing specific guidelines for applying for a LTO.
The guidelines set out the requirements for initial LTOs, as well as for renewals and variations of licenses. Initial LTO applications require the most documentation. FDA expects applicants to provide materials such as an eApplication form with a declaration of undertaking and proof of business name registration. Manufacturers must also supply proof of capitalization, a site master file, floor plan and risk management plan.
FDA said, “Valid applications should be owned by the licensed establishment or the owner/president/CEO” and as such, “Online transactions shall not be entrusted to a person who is not the duly authorized person.” The agency does not consider consultants, liaison officers and freelancers to be authorized or qualified persons.
After an application is submitted, an evaluator from the relevant FDA center will pre-assess the materials and reject incomplete submissions. The draft also lists various instances that are grounds for disapproval even if all the documentation is present, such as the failure to meet the required technical requirements and the violation of the terms of the license.
Pre-license facility inspections are mandatory for all manufacturers before the granting of an initial LTO. FDA will also perform inspections before signing off on certain LTO variations. The agency will outline the parameters for inspection in separate documents.
The draft is open for comment until 2 June.
Draft Guidelines
Pakistan’s DRAP starts consultation on good distribution practices for drugs, biologicals
The Drug Regulatory Authority of Pakistan (DRAP) is seeking feedback on its proposed good distribution practices (GDPs) for pharmaceutical and biological products. Once adopted, the GDP guideline will apply to all manufacturers, importers and other players involved in the supply of drug products.
DRAP is creating the guidelines to ensure the integrity and quality of drug products. To achieve that goal, the agency has outlined principles for safe storage and distribution and the roles and responsibilities of people at each link in the supply chain. DRAP has broken the text up into sections on quality management, personnel, premises and equipment, documentation, operations and other topics.
Building on the Pharmaceutical Inspection Co-operation Scheme’s (PIC/S) 2014 Guide to Good Distribution Practices for Medicinal Products, DRAP starts the document with an overview of quality management topics, outlining the quality system requirements and the purpose of a change control system.
Some sections of the draft are copied directly from the PIC/S guide, but DRAP has also rewritten parts and added new content. Examples of additions made by DRAP include lines about cold chain practices, warranty invoices and specialized clothing.
DRAP, which uploaded the draft on 28 May, is accepting feedback for 15 days.
DRAP Notice
TGA updates guidance on testimonials and endorsements in advertising as transition nears end
TGA has updated its guidance on testimonials and endorsements in advertising ahead of starting to enforce the new code at the end of June. The updated guidance reflects changes to the TGA’s position on forms of advertising, including paid testimonials from influencers.
As the guidance explains, the code prohibits testimonials from anyone who has received “valuable consideration” for their contribution. The prohibition extends to social media influencers, bloggers and brand ambassadors.
TGA sets out the implications in examples of a health and well-being Instagram influencer who receives an all-expenses-paid trip to attend the launch of a multivitamin and a men’s health blogger who receives a free six-month supply of a product on the proviso that he writes a testimonial. In both scenarios, the companies cannot use testimonials from the influencers in their advertising.
TGA Guidance


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