Reasons for rejection of applications for medical devices
The TGA notes that the rate of rejection or lapsing of applications to include medical devices in the Australian Register of Therapeutic Goods (ARTG) remains at approximately 20% and has not dropped significantly in the 4 years of operation of the new regulatory scheme.
We have therefore developed the following list of reasons for rejection in order that sponsors may consider their readiness prior to submitting an application.
Applications submitted through DEAL
Applications submitted through DEAL (for Class I, Class IIa and Class IIb devices) are rejected because of
- incorrect information in the "Specific Details" section of the DEAL application;
- [This section contains a number of questions about the device - the answers default to "No" if not specifically answered. Sponsors often gloss over this section, resulting in a "No" answer to all questions, often incorrectly. An error in this section, particularly for Class I devices, will lead to automatic rejection.]
- incorrect classification;
- [sponsors are reminded that it is the manufacturer's responsibility to classify a device and sponsors should not guess at the classification. Guidance on classification is found in Guidance Document 25 <http://www.tga.gov.au/docs/html/devguid25.htm>.
- incorrect GMDN code selection;
- [guidance on the application of GMDN codes is found in Fact Sheet 18 <http://www.tga.gov.au/devices/fs_gmdn.htm>.
- GMDN definition does not align itself with the manufacturer's intended purpose;
- incorrect application selection;
- [eg IVD submitted as an included medical device] or
- the product is required to undergo a TGA Conformity Assessment prior to application submission
Applications subject to Application Audit
Applications subject to Application Audit (Class III and AIMD devices, in the main) are rejected or lapse because:
- The supporting data is not supplied within the specified time-frame;
- [When filing the DEAL application, a sponsor certifies that he/she either holds the information related to the device, or can obtain it from the manufacturer within 20 days. The Application Audit process tests this certification. Sponsors of Class III and AIMD devices should be aware that the application will always be subject to audit. The information required for the audit process is specified in Guidance Document 2 <http://www.tga.gov.au/docs/html/devguid2.htm>. A sponsor should not submit the application until all the required information is available.]
- Failure to provide key documents (see above link to Guidance Document 2 for the list of documents required), or properly notarised copies of original documents;
- Problems with the clinical evidence;
- [The TGA requires only the clinical Expert Report - the summary and appraisal of the clinical evidence that supports the device. In many cases, this report does not exist, is not signed or has not been written by an appropriately qualified expert. Guidance on what is required in an Expert Report and who is qualified to write the report is included in Guidance Document 4 <http://www.tga.gov.au/docs/html/devguid4.htm>. However, it is the manufacturer's responsibility to enure that this report has been generated and assessed during the CE certification process. It should not be generated by the sponsor at the time of application to TGA.]
- Information supplied is not in English;
- A Declaration of Conformity to Australian requirements has not been supplied;
- [Manufacturers will supply to sponsors the Declaration of Conformity to European requirements prepared in accordance with the European Medical Devices Directive. However, the manufacturer is required to take into account that the device is to be supplied in Australia and consider whether Australian conditions and Australian regulatory requirements impact on the device's compliance with the Essential Principles. The manufacturer must prepare a DoC to Australian requirements. Guidance on the DoC may be found in Guidance Document 5 <http://www.tga.gov.au/docs/html/devguid5.htm>.
- The device contains material of animal, recombinant or microbial origin, or a medicinal substance and therefore is not eligible for the application audit process;
- [The manufacturer of these types of devices must have a conformity assessment certificate issued by the TGA.]
- Sterilisation validation reports do not relate to the device which is the subject of the application, or to the relevant manufacturing site;
- There is no evidence of close-out of non-conformities from the last audit of the manufacturer's Quality Management System.
Applications for conformity assessment
Applications for Conformity Assessment (Australian manufacturers, all manufacturers of devices containing a medicinal substance, or material of animal origin or microbial or recombinant origin).
The TGA tends to work with Australian manufacturers who are going through the conformity assessment process for the first time to resolve problems rather than reject the application. However, the major areas of deficiency are:
- The manufacturer is not ready for audit at the time the application is submitted. Manufacturers should not submit the application until the Quality Management System is fully developed and they are ready for an on-site audit. Note: ISO 9001 certification or compliance is a poor benchmark for the necessary ISO 13485 compliance;
- Lack of clinical evidence, or Expert Report not prepared (see Guidance Document 4 <http://www.tga.gov.au/docs/html/devguid4.htm>);
- Lack of biocompatibility data, or an expert assessment justifying a decision not to conduct biocompatibility testing;
- Electromedical safety and/or Electromagnetic Compatibility (EMC) testing incomplete;
- Device software or control system not validated;
- Critical production processes not validated (e.g. cleaning, sterilisation, coating and production software);
- Outsourced production processes or services not controlled;
- The application is made by someone other than the responsible manufacturer (eg an OEM subcontractor who does not take responsibility for the device);
- The manufacturer has not addressed all of the Essential Principles relevant to the device, or does not have supporting data to substantiate compliance claims;
- Risk analyses do not consider the clinical use of the device (e.g. OH&S risk management only without consideration of the end patient, and/or no clinical expertise input to risk analysis);
- The full product life-cycle not considered in risk management (e.g. risks arising from production processes, integration with quality management system and post market surveillance);
- Implementation and effectiveness of risk control measures not verified (eg purchasing controls, fail-safe mechanisms, warnings on labels).
Applications for conformity assessment which have a Design Examination component (Class III and AIMDs) will normally be considered by the Medical Device Evaluation Committee (MDEC) prior to a decision on approval. The MDEC is particularly concerned at the number of applications presenting with poor clinical evidence. The TGA has rejected applications on the basis of;
- Poorly supported claims of equivalence to existing approved devices;
- [The TGA will accept claims of equivalence, but those claims must be well supported before the clinical evidence for the existing device can be used to support the new device. Equivalence must be demonstrated through bench testing or device specifications. Claims of material equivalence must be well supported.]
- Clinical evidence presented was not relevant to the device;
- [Clinical data for a predicate device will be accepted as supporting data if claims of equivalence are well supported, but evidence for the device itself must be available. Post-market data is acceptable as evidence.]
- Where clinical trial evidence was presented, that evidence was inadequate, eg the numbers of patients were too low to provide the required statistical evidence of performance. In some cases, the totality of clinical evidence was not presented to the TGA, for instance where clinical trials were underway or had been completed in the US at the request of the FDA, or post-market data resulting from several years' supply in Europe was available, but not presented.