Understanding TGA Application Audits for ARTG Inclusion

While not all applications for inclusion of a device on the Australian Register of Therapeutic Goods (ARTG) are subject to a detailed review by the Therapeutic Goods Administration (TGA), some may be subject to such a review known as an audit assessment. This article provides an overview of the audit assessment process, including the documentation to be presented to the TGA and relevant timeframes, as well as as well as strategic considerations for manufacturers looking to expand into the Australian market.

Will My Application Be Subject to an Audit?

Application audits may be mandatory for certain types of devices or may be at the discretion of the TGA. Those devices (including systems and procedure packs) subject to mandatory audits are prescribed under Regulation 5.3 of the Therapeutic Goods (Medical Devices) Regulations 2002 and include: 

• • Barrier devices (other than condoms) indicated for contraception or prevention of the transmission of disease in the course of penile penetration during sexual intercourse 
  • Implantable contraceptive devices 
  • Spinal fusion implantable device (Including screws, cages, plates, hooks, or rods that are intended to be used during spinal fusion surgical procedures) 
  • Devices specifically intended by the manufacturer to be used for disinfecting another medical device 
  • Implantable intraocular lenses 
  • Intraocular viscoelastic fluids 
  • Class III medical devices that have not been assessed under the EC Mutual Recognition Agreement or the EFTA Mutual Recognition Agreement 

Any of the following in vitro diagnostic medical devices (IVDs): 

• • Non-assay-specific quality control materials intended for monitoring a Class 4 IVD medical device; 
  • Self-testing IVDs 
  • Point-of-care IVDs 
  • Class 3 IVDs intended for detecting the presence of, or exposure to, a sexually transmitted agent 
  • IVDs for managing or monitoring the treatment of infections diagnosed using a Class 4 IVD (e.g. quantitative nucleic acid test (NAT) and genotyping assays for HIV and HCV) 
  • IVDs intended to be supplied for use under the Pharmaceutical Benefits Scheme (PBS) 
  • IVDs intended to be supplied for use in a national screening program 
  • IVDs that the TGA is not satisfied that have been manufactured in a location and at a site where a body or authority has exercised its authority and expertise to perform conformity assessment (e.g. inspection audit) 

(NOTE: This does not apply to IVDs for which a Conformity Assessment Certificate (CAC), or an Australian Conformity Assessment Body Certificate has been issued, and has not been suspended or revoked with respect to the IVD) 

• • Class 4 IVDs, including Class 4 in-house IVDs 
  • Companion diagnostic IVDs 

If a manufacturer of one of the types of devices listed above can fulfill one of the following conditions, the device is not subject to mandatory auditing:

• • Hold a TGA CAC for the device 
  • Hold an EU MDR 2017/745 or IVDR 2017/746 certificate that has not been suspended or revoked 
  • The device is included in the ARTG as an export-only device or export-only IVD

Outside of the above-listed devices, at the discretion of the TGA, any application may be selected for an audit with some specific types of devices more likely to be selected than others (e.g. software-based medical devices).

Such applications are typically based upon a risk-based approach applied by the regulator to verify several details of the device in the application, including:

• • Appropriate qualification/classification 
  • Benefit-risk analysis 
  • Presence of any false or misleading information, and the completeness/accuracy of information in the application 
  • Adequacy of information to demonstrate conformity with the Essential Principles and/or conformity assessment procedures 
  • The presence of any substances prohibited from importation under the Customs Act 1901 

TGA Notification of Application Audit

When selected for an application audit, the Australian Sponsor that applied will be notified within twenty days of application fee payment via a notification letter issued by the TGA by Section 41FH of the Therapeutic Goods Act 1989 which outlines the information to be provided, timeframe in which this information is to be provided (generally 10-20 working days) and, where applicable, any audit assessment fee to be paid (only mandatory audits are subject to assessment fees). It is important to note that where the applicable fee and information requested are not provided in the requested timeframe (an additional allowance of 10 working days is applicable), the application will lapse without the application fee being refunded. 

The type of supporting documentation requested and to be submitted depends upon the level of audit indicated in the notification letter (as determined by the TGA), and may include the following (although in the case of IVDs, there is only one type of audit assessment, known as a technical file review): 

The documentation requested for IVD technical file reviews includes:

• • Manufacturer’s DoC 
  • Conformity assessment evidence for the IVD and manufacturer (e.g. Quality assurance, Design examination, Type examination certificates) 
  • Summary Technical Documentation (STED), including the clinical evidence report (i.e. using EU IVDR 2017/746 terminology, the Performance Evaluation Report) 

TGA Application Audit Assessment

While there are no legislated timeframes for the TGA to complete application audits, annual regulator performance reports which include data on TGA application processing timeframes are published and available on the regulator’s website.

The time necessary for the TGA to perform the application audit typically depends on several factors including: 

• • Availability of TGA reviewer resources 
  • Time taken to pay any applicable audit assessment fees and provide the information requested 
  • The quality of information provided to the TGA (The TGA can request additional information under what is known as a 41JA request (like an FDA Additional Information request)) 

While the application is undergoing assessment, Australian Sponsors may submit a request to withdraw the application, or it may lapse (with no refund of fees paid under either circumstance). In a similar manner to initial notification of audit assessment, any failure to provide the TGA with a response to a 41JA request within a further 10 working days from the day specified in the notice letter or provision of false or misleading information can result in a lapse of the submission. This is also applicable where an audit assessment fee has not been paid within 28 days after the day that the Australian Sponsor was notified of the fee. 

Upon conclusion of its application audit assessment, the TGA will notify the Australian Sponsor of either of the following outcomes: 

The decision to include the kind of device in the ARTG : This outcome results in the publication of the ARTG certificate of inclusion for the device and compliance with the ongoing responsibilities for device inclusion on the register. 

• • The decision not to include the kind of device in the ARTG : Written notification will be provided by the TGA outlining the reasons for not including the device in the register as well as information on the appeal process although a new application for inclusion on the ARTG can be submitted at any time. 

Strategic Considerations for Market Expansion

For IVD manufacturers looking to expand into the Australian market after obtaining authorization in a major market such as the EU, it’s important to understand that while the Australian and European regulatory systems share similarities that facilitate the registration process, they are not equivalent. Australia has its own requirements and a strict set of conformity assessment rules your product must meet before you can register with the TGA.

Depending on your IVD’s classification, characteristics, or regulatory history, it may also be subject to a technical file review or application audit, in which the TGA requests a separate submission of specific documentation for a more rigorous review. Advanced preparation can help you meet the audit deadline and documentation requests. However, your device can still be selected for a mandatory application audit even if it does not meet the criteria for mandatory audits. TGA may enforce an application audit to ensure your certification body is acceptable and that they have conducted the appropriate conformity assessment procedures according to your IVD’s classification.

TGA will look at the certification body’s accreditation, the Annex Route (for EC Certificates), the Directive or Regulation, and the scope of your certification to determine if your quality system and/or conformity assessment evidence is acceptable. An EC Certificate must articulate the appropriate requirements for your device to be acceptable. Note that TGA no longer accepts ISO 13485 certificates (with few exceptions) for new IVD applications. Schedule 3 of the Therapeutic Goods Regulations 2002 describes the required conformity assessment procedures for each IVD classification.

Preparing Your Submission for a TGA Application Audit

Even if you know your IVD will require a mandatory application audit, you must wait until TGA notifies you of the audit before compiling and submitting your evidence. The notification from TGA will specify the evidence they require. However, manufacturers should expect to provide the following:

• • Australian Declaration of Conformity (DoC)
  • Conformity assessment evidence for the IVD and the manufacturer
  • Technical File in Summary Technical Documentation (STED) format
  • Labeling
  • Instructions for Use (IFU)
  • Advertising and marketing materials (brochures, advertisements, etc.)
  • Additional documentation as requested (e.g., evidence of accurate classification, etc.)

If you are leveraging an EC Certificate for your TGA registration, your audit submission may also include your Performance Evaluation Report (PER) and risk management file, along with your EU labeling. However, if you are leveraging US FDA clearance without an MDSAP certificate, the application audit might be more cumbersome as there are fewer similarities between FDA and TGA regulatory structures and documentation types. In this case, you may be required to submit evidence of conformity with clinical evidence under Essential Principle 14, which establishes the requirement for clinical evaluation procedures, and an Essential Principles Checklist.

TGA will expect more detailed evidence in each section of your technical file if your IVD is higher risk. Sections beyond the device history and device descriptions for Class 3 and 4 IVDs should be detailed as opposed to a summary. For Class 4 IVDs, TGA will expect an elaborated Clinical Evidence section.
Your documentation should be provided as a complete stand-alone submission. TGA will not accept submissions that cross-reference previous or in-progress applications. Doing so could result in a lapse or application failure.

Ready for the next step?

This article provides an overview of TGA application audits. If you have any questions regarding Australian medical device regulatory requirements or require an Australian Sponsor, get in touch. 

If you’re thinking about expanding to Australia, it’s important to understand how their conformity assessment procedures apply to your IVD, especially if you are marketing a higher risk IVD. Any oversight could lead to regulatory delays, an application audit, or, potentially, a required TGA certificate, even if you already have authorization in another market. Your Australian TGA Sponsor will be an invaluable resource during the registration and audit process, as they can review your conformity assessment evidence before submission and advise you if any gaps exist.

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